Abstract
Innate immunity mediates strong resistance to fungal pathogens and contributes to host defense against opportunistic fungal infections such as candidiasis, aspergillosis, and other rare infections. Immune factors such as cytokines and effector immune cells work synergistically with antifungal agents to restrict fungal growth. However, in immunocompromised hosts, the defectiveness of immune functions that should cooperate with antifungal drugs to clear the pathogens seems to be a critical factor that impedes the effectiveness of these drugs. The renovation or augmentation of immune responses is now considered as one of the foundations of effective antifungal therapy. Immunomodulation represents a novel approach to antimicrobial therapy that depends on boosting host immunity, rather than direct antimicrobial activity. Immunopotential therapy therefore offers a rational approach to the treatment of fungal infections, because it is intended to enhance immune functions in general. Major advances in the field of experimental immunology have provided insight into the important regulatory role of cytokines in both innate and adaptive immunity to fungal pathogens. Exploration has also begun with immunotherapy, with use of cytokines and immunomodulators alone or in combination with antifungal therapy. The administration of cytokines to patients, together with antifungal agents, offers promising immuno-therapeutic modalities for further research. The diverse array of natural, synthetic, and recombinant immunomodulators discussed in this chapter succinctly demonstrates the potential of these agents to stimulate host defense mechanisms for prophylaxis and treatment of various fungal infections.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Agarwal M, Walia S, Dhingra S, Khambay BPS (2001) Insect growth inhibition, antifeedant and antifungal activity of compounds isolated/derived from Zingiber officinale Roscoe (ginger) rhizomes. Pest Manag Sci 57:289–300
Ahn K, Woong SS, Hwan MK, Sang BH, Kim IH (1998) Biotech letters 20(1):5–7
Armitage JO (1998) Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor. Blood 92:4491–4508
Arruda C, Franco MF, Kashino SS, Nascimento FR, Fazioli Rdos A, Vaz CA, Russo M, Calich VL (2002) Interleukin-12 protects mice against disseminated infection caused by Paracoccidioides brasiliensis but enhances pulmonary inflammation. Clin Immunol 103:185–195
Barbaric D, Shaw PJ (2001) Scedosporium infection in immunocompromised patients: successful use of liposomal amphotericin B and itraconazole. Med Pediatr Oncol 37:122–125
Bauman SK, Huffnagle GB, Murphy JW (2003) Effects of tumor necrosis factor alpha on dendritic cell accumulation in lymph nodes draining the immunization site and the impact on the anticryptococcal cell-mediated immune response. Infect Immun 71:68–74
Bensky D, Gamble A (1993) Chinese herbal medicine; materica medica (revised edition). Eastland Press, Seattle, USA
Bomford R (1988) Immunomodulators from plants and fungi. Phytother Res 2(4):159–164
Boneberg EM, Hareng L, Gantner F, Wendel A, Hartung T (2000) Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-gamma. Blood 95:270–276
Brieland JK, Jackson C, Menzel F, Loebenberg D, Cacciapuoti A, Halpern J et al (2001) Networking in lungs of immunocompetent mice in response to inhaled Aspergillus fumigatus. Infect Immun 69:1554–1560
Casadevall A, Pirofski LA (2001) Adjunctive immune therapy for fungal infections. Clin Infect Dis 33:1048–1056
Casadevall A, Cleare W, Feldmesser M, Glatman-Freedman A, Kozel TR, Lendvai N, Mukherjee J, Pirofski L, Rivera J, Rosas AL et al (1998) Characterization of a murine monoclonal antibody to C. neoformans polysaccharide which is a candidate for human therapeutic studies. Antimicrob Agents Chemother 42:1437–1446
Cenci E, Bartocci A, Puccetti P, Mocci S, Stanley ER, Bistoni F (1991) Macrophage colony-stimulating factor in murine candidiasis: serum and tissue levels during infection and protective effect of exogenous administration. Infect Immun 59:868–872
Cenci E, Romani L, Mencacci A, Spaccapelo R, Schiaffella E, Puccetti P, Bistoni F (1993) Interleukin-4 and interleukin-10 inhibit nitric oxide-dependent macrophage killing of Candida albicans. Eur J Immunol 23:1034–1038
Cenci E, Mencacci A, Fe d’Ostiani C, Del Sero G, Mosci P, Montagnoli C, Bacci A, Romani L (1998) Cytokine- and T helper-dependent lung mucosal immunity in mice with invasive pulmonary aspergillosis. J Infect Dis 178:1750–1760
Cenci E, Mencacci A, Del Sero G, Bacci A, Montagnoli C, d’Ostiani CF et al (1999) Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses. J Infect Dis 180:1957–1968
Centeno-Lima S, Silveira H, Casimiro C, Aguiar P, do Rosario VE (2002) Kinetics of cytokine expression in mice with invasive aspergillosis: lethal infection and protection. FEMS Immunol Med Microbiol 32:167–173
Chiller T, Farrokhshad K, Brummer E, Stevens DA (2001) The interaction of human monocytes, monocyte-derived macrophages, and polymorphonuclear neutrophils with caspofungin (MK-0991), an echinocandin, for antifungal activity against Aspergillus fumigatus. Diagn Microbiol Infect Dis 39:99–103
Chiller T, Farrokhshad K, Brummer E, Stevens DA (2002) Effect of granulocyte colony-stimulating factor and granulocyte–macrophage colony stimulating factor on polymorphonuclear neutrophils, monocytes or monocyte-derived macrophages combined with voriconazole against Cryptococcus neoformans. Med Mycol 40:21–26
Clemons KV, Stevens DA (2001) Overview of host defense mechanisms in systemic mycoses and the basis for immunotherapy. Semin Respir Infect 16:60–66
Clemons KV, Lutz JE, Stevens DA (2001) Efficacy of recombinant gamma interferon for treatment of systemic cryptococcosis in SCID mice. Antimicrob Agents Chemother 45:686–689
Clemons KV, Grunig G, Sobel RA, Mirels LF, Rennick DM, Stevens DA (2000) Role of IL-10 in invasive aspergillosis: increased resistance of IL-10 gene knockout mice to lethal systemic aspergillosis. Clin Exp Immunol 122:186–191
Committee on New Directions in the Study of Antimicrobial Therapeutics (2006) Immunomodulation: treating infectious diseases in a microbial world: report of two workshops on novel antimicrobial therapies. National Academies Press, Washington, DC
Constantopoulos A, Najjar VA, Smith JW (1972) Tuftsin deficiency: a new syndrome with defective phagocytosis. J Pediat 80:564–572
Constantopoulos A, Najjar V, Wish JB, Necheles TH, Stolbach LL (1973) Defective phagocytosis due to tuftsin deficiency in splenectomized subjects. Am J Dis Child 125:663–665
Coste A, Linas MD, Cassaing S, Bernad J, Chalmeton S, Seguela JP, Pipy B (2002) A sub-inhibitory concentration of amphotericin B enhances candidastatic activity of interferon-gamma- and interleukin-13- treated murine peritoneal macrophages. J Antimicrob Chemother 49:731–740
Decken K, Kohler G, Palmer-Lehmann K, Wunderlin A, Mattner F, Magram J, Gately MK, Alber G (1998) Interleukin-12 is essential for a protective Th1 response in mice infected with Cryptococcus neoformans. Infect Immun 66:4994–5000
Deepe GS Jr, Gibbons R (2000) Recombinant murine granulocyte–macrophage colony-stimulating factor modulates the course of pulmonary histoplasmosis in immunocompetent and immunodeficient mice. Antimicrob Agents Chemother 44:3328–3336
Deepe GS Jr, Gibbons RS (2003) Protective and memory immunity to Histoplasma capsulatum in the absence of IL-10. J Immunol 171(10):5353–5362
de Oliveira SM, Torres TC, Pereira SL, Mota OM, Carlos MX (2008) Effect of a dentifrice containing Aloe vera on plaque and gingivitis control: A double-blind clinical study in humans. J Appl Oral Sci 16(4):293–296
Del Sero G, Mencacci A, Cenci E, d’Ostiani CF, Montagnoli C, Bacci A et al (1999) Antifungal type 1 responses are upregulated in IL-10-deficient mice. Microbes Infect 1:1169–1180
Djeu JY, Blanchard DK, Halkias D et al (1986) Growth inhibition of C. albicans by human polymorphonuclear neutrophils; activation by interferon and tumour necrosis factor. J Immunol 137:2480–2484
Egger SF, Brown GS, Kelsey LS, Yates KM, Rosenberg LJ, Talmadge JE (1996) Int J Immunopharm 18(2):113–126
Eggimann P, Garbino J, Pittet D (2003) Management of Candida species infections in critically ill patients. Lancet Infect Dis 3(12):772–785
Elgayyar M, Draughon FA, Golden DA, Mount JRJ (2001) Antimicrobial activity of essential oils from plants against selected pathogenic and saprophytic microorganisms. J Food Prot 64(7):1019–1024
Ellis M, Watson R, McNabb A, Lukic ML, Nork M (2002) Massive intracerebral aspergillosis responding to combination high dose liposomal amphotericin B and cytokine therapy without surgery. J Med Microbiol 51:70–75
Feily A, Namazi MR (2009) Aloe vera in dermatology: a brief review. G Ital Dermatol Venereol 144:84–91
Feldmesser M, Mukherjee J, Casadevall A (1996) Combination of 5-flucytosine and capsule-binding monoclonal antibody in the treatment of murine Cryptococcus neoformans infections and in vitro. J Antimicrob Chemother 37:617–622
Franzke A, Piao W, Lauber J, Gatzlaff P, Konecke C, Hansen W et al (2003) G-CSF as immune regulator in T cells expressing the G-CSF receptor: implications for transplantation and autoimmune diseases. Blood 102:734–739
Fridkin M, Gottlieb P (1981) Tuftsin, Thr-Lys-Pro-Arg. Anatomy of an immunologically active peptide. Mol Cell Biochem 41:73–97
Gaviria JM, van Burik JA, Dale DC, Root RK, Liles WC (1999) Comparison of interferon-gamma, granulocyte colony-stimulating factor, and granulocyte–macrophage colony-stimulating factor for priming leukocyte-mediated hyphal damage of opportunistic fungal pathogens. J Infect Dis 179:1038–1041
Ghannoum MA (2001) Candida: a causative agent of an emerging infection. J Investig Dermatol 6:188–196
Gildea LA, Gibbons R, Finkelman FD, Deepe GS Jr (2003) Overexpression of interleukin-4 in lungs of mice impairs elimination of Histoplasma capsulatum. Infect Immun 71:3787–3793
Gil-Lamaignere C, Maloukou A, Winn RM, Panteliadis C, Roilides E (2001) The Eurofung Network. Effects of interferon-gamma and granulocyte–macrophage colony-stimulating factor on human neutrophil-induced hyphal damage of Scedosporium spp. Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago. Abstract J-469
Gil-Lamaignere C, Roilides E, Maloukou A, Georgopoulou I, Petrikkos G, Walsh TJ (2002a) Amphotericin B lipid complex exerts additive antifungal activity in combination with polymorphonuclear leucocytes against Scedosporium prolificans and Scedosporium apiospermum. J Antimicrob Chemother 50:1027–1030
Gil-Lamaignere C, Roilides E, Mosquera J, Maloukou A, Walsh TJ (2002b) Antifungal triazoles and polymorphonuclear leukocytes synergize to cause increased hyphal damage to Scedosporium prolificans and Scedosporium apiospermum. Antimicrob Agents Chemother 46:2234–2237
Gonzalez GM, Tijerina R, Najvar LK, Bocanegra R, Luther M, Rinaldi MG, Graybill JR (2001) Correlation between antifungal susceptibilities of Coccidioides immitis in vitro and antifungal treatment with caspofungin in a mouse model. Antimicrob Agents Chemother 45:1854–1859
Gottlieb P, Beretz A, Fridkin M (1982) Tuftsin analogs for probing its specific receptor site on phagocytic cells. Eur J Biochem 125:631–638
Groll AH, Walsh TJ (2001) Uncommon opportunistic fungi: new nosocomial threats. Clin Microbiol Infect 7(Suppl 2):8–24
Groll AH, Walsh TJ (1999) Azoles: Triazoles. In: Yu VL et al (eds) Antimicrobial Therapy and Vaccines, 1st edn. Williams and Wilkins, Philadelphia, pp 1158–1165
Gupta CM, Haq W (2005) Tuftsin-bearing liposomes as antibiotic carriers in treatment of macrophage infections. Methods Enzymol 391:291–304
Gupta CM, Puri A, Jain RK, Bali A, Anand N (1986) Protection of mice against Plasmodium berghei infection by a tuftsin derivative. FEBS Lett 205:351–354
Guru PY, Agrawal AK, Singha UK, Singhal A, Gupta CM (1989) Drug targeting in Leishmania donovani infections using tuftsin-bearing liposomes as drug vehicles. FEBS Lett 245:204–208
Hajjeh RA, Warnock DW (2003) Epidemiology of systemic fungal diseases: overview. In: Dismukes WE, Pappas PG, Sobel JD (eds) Clinical Mycology. Oxford University Press, New York, pp 23–30
Hori Y, Miura T, Hirai Y, Fukumura M, Nemoto Y, Toriizuka K, Ida Y (2003) Pharmacognostic studies on ginger and related drugs – part 1: five sulfonated compounds from Zingeberis rhizome (Shokyo). Phytochemistry 62:613–617
Jae KL, Myung KL, Yeo PY, Young SK, Jong SK, Yeong SK, Kyung JK, Seong SH, Chong-kil L (2001) Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells. Int Immunopharm 1(7):1275–1284
Kawakami K, Qureshi MH, Koguchi Y, Zhang T, Okamura H, Kurimoto M, Saito A (1999a) Role of TNF-alpha in the induction of fungicidal activity of mouse peritoneal exudate cells against Cryptococcus neoformans by IL-12 and IL-18. Cell Immunol 193:9–16
Kawakami K, Qureshi MH, Zhang T, Koguchi Y, Xie Q, Kurimoto M, Saito A (1999b) Interleukin-4 weakens host resistance to pulmonary and disseminated cryptococcal infection caused by combined treatment with interferon-gamma-inducing cytokines. Cell Immunol 197:55–61
Kawakami K, Koguchi Y, Qureshi MH, Kinjo Y, Yara S, Miyazato A et al (2000a) Reduced host resistance and Th1 response to Cryptococcus neoformans in interleukin-18 deficient mice. FEMS Microbiol Lett 186:121–126
Kawakami K, Qureshi MH, Zhang T, Koguchi Y, Yara S, Takeda K et al (2000b) Involvement of endogenously synthesized interleukin (IL)-18 in the protective effects of IL-12 against pulmonary infection with Cryptococcus neoformans in mice. FEMS Immunol Med Microbiol 27:191–200
Khan ZK, Jain P (2000) Antifungal agents and Immunomodulators in systemic mycoses. Indian J Chest Dis Allied Sci 42:345–3551
Khan MA, Owais M (2005) Immunomodulator tuftsin increases the susceptibility of Cryptococcus neoformans to liposomal amphotericin B in immunocompetent BALB/c mice. J Drug Target 13(7):423–429
Khan MA, Owais M (2006) Toxicity, stability and pharmacokinetics of amphotericin B in immunomodulator tuftsin-bearing liposomes in a murine model. J Antimicrob Chemother 58(1):125–132
Khan MA, Syed FM, Nasti HT, Saima Dagger K, Haq W, Shehbaz A, Owais M (2003) Use of tuftsin bearing nystatin liposomes against an isolate of Candida albicans showing less in vivo susceptibility to amphotericin B. J Drug Target 11(2):93–99
Khan MA, Nasti TH, Saima K, Mallick AI, Firoz A, Wajahul H, Ahmad N, Mohammad O (2004) Co-administration of immunomodulator tuftsin and liposomised nystatin can combat less susceptible Candida albicans infection in temporarily neutropenic mice. FEMS Immunol Med Microbiol 41(3):249–258
Khan MA, Ahmad N, Moin S, Mannan A, Wajahul H, Pasha ST, Khan A, Owais M (2005a) Tuftsin-mediated immunoprophylaxis against an isolate of Aspergillus fumigatus shows less in vivo susceptibility to amphotericin B. FEMS Immunol Med Microbiol 44(3):269–276
Khan MA, Nasti TH, Owais M (2005b) Incorporation of amphotericin B in tuftsin-bearing liposomes showed enhanced efficacy against systemic cryptococcosis in leucopenic mice. J Antimicrob Chemother 56(4):726–731
Khan MA, Faisal SM, Mohammad O (2006) Safety, efficacy and pharmacokinetics of tuftsin-loaded nystatin liposomes in murine model. J Drug Target 14(4):233–241
Khan ZK, Manglani A, Shukla PK et al. (1995) Immunomodulatory effect of plant extracts and iridoid glucosides from Nyctanthes arbortristis against systemic candidiasis in mice. Int J Pharmacog 33:297–304
Khemani S, Brummer E, Stevens DA (1995) In vivo and in vitro effects of macrophage colony-stimulating factor (M-CSF) on bronchoalveolar macrophages for anti-histoplasmal activity. Int J Immunopharmacol 17:49–53
Kontoyiannis D, Wessel V, Bodey G, Rolston K (2000) Zygomycosis in the 1990s in a tertiary care center. Clin Infect Dis 30:851–856
Kudeken N, Kawakami K, Saito A (1999) Cytokine-induced fungicidal activity of human polymorphonuclear leukocytes against Penicillium marneffei. FEMS Immunol Med Microbiol 26:115–124
Kuhara T, Uchida K, Yamaguchi H (2000) Therapeutic efficacy of human macrophage colony-stimulating factor, used alone and in combination with antifungal agents, in mice with systemic Candida albicans infection. Antimicrob Agents Chemother 44:19–23
Kullberg BJ (1997) Trends in immunotherapy of fungal infections. Eur J Clin Microbiol Infect Dis 16:51–55
Kurt-Jones EA, Mandell L, Whitney C, Padgett A, Gosselin K, Newburger PE, Finberg RW (2002) Role of toll-like receptor 2 (TLR2) in neutrophil activation: GM-CSF enhances TLR2 expression and TLR2-mediated interleukin 8 responses in neutrophils. Blood 100:1860–1868
Labro MT (1998) Antibacterial agents — phagocytes: new concepts for old in immunomodulation. Int J Antimicrob Agents 10:11–21
Larsen RA, Pappas P, Perfect J, Aberg JA, Casadevall A, Dismukes WE (2002) The National Institute of Allergy and Infectious Diseases (NIAID) and the Mycoses Study Group. Passive immunization for therapy: the MSG 43 study. Fifth International Conference on Cryptococcus and Cryptococcosis, Adelaide, Australia. Abstract S3.3
Larsen RA, Pappas PG, Perfect J, Aberg JA, Casadevall A, Cloud GA, James R, FIller S, Dismukes WE (2005) Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob Agents Chemother 49:952–958
Latge JP (1999) Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 12:310–350
Latham PW (1999) Therapeutic peptides revisited. Nat Biotechnol 17:755–757
Lutz JE, Clemons KV, Stevens DA (2000) Enhancement of antifungal chemotherapy by interferon-gamma in experimental systemic cryptococcosis. J Antimicrob Chemother 46:437–442
Lyman CA, Garrett KF, Pizzo PA, Walsh TJ (1994) Response of human polymorphonuclear leukocytes and monocytes to Trichosporon beigelii: host defense against an emerging opportunistic pathogen. J Infect Dis 170:1557–1565
Martino R, Subira M (2002) Invasive fungal infections in hematology: new trends. Ann Hematol 81:233–243
Martins AP, Salguelro L, Goncalves MJ, Proenca da Cunha A, Vila R, Cafigueral S, Mazzoni V, Tomi F, Casanova J (2001) Essential oil composition and antimicrobial activity of three Zingiberaceae from S. Tomee principe. J Planta Med 67:580–584
Masihi KN (1994a) Cytokines and immunomodulators: promising therapeutic agents. Parasitol Today 10:1–2
Masihi KN (ed) (1994b) Immunotherapy of Infections. Marcel Dekker, New York
Masihi KN (1996) Immunotherapy of microbial diseases. In: Hadden JW, Szentivanyi A (eds) Immunopharmacol reviews. Plenum, New York, pp 157–199
Masihi KN (ed) (1997) Special issue: First European Conference on Immunopharmacology. 26–29 May 1997, Berlin. Int J Immunopharmacol 19:463–617
Masihi KN, Lange W (1988) Immunomodulators and nonspecific host defence mechanisms against microbial infections. Pergamon, Oxford
Masihi KN, Lange W (eds) (1990) Immunotherapeutic prospects of infectious diseases. Springer, Berlin
Masood AK, Owais M (2006) Toxicity, stability and pharmacokinetics of amphotericin B inimmunomodulator tuftsin-bearing liposomes in a murine model. J Antimicrob Chemother 58:125–132
Matthews R, Burnie J (2001) Antifungal antibodies: a new approach to the treatment of systemic candidiasis. Curr Opin Investig Drugs 2:472–476
Matthews RC, Rigg G, Hodgetts S, Carter T, Chapman C, Gregory C, Illidge C, Burnie J (2003) Preclinical assessment of the efficacy of Mycograb, a human recombinant antibody against fungal HSP90. Antimicrob Agents Chemother 47:2208–2216
McNeil MM, Nash SL, Hajjeh RA, Phelan MA, Conn LA, Plikaytis BD, Warnock DW (2001) Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 33:641–647
Mejias A, Chavez-Bueno S, Rios AM, Saavedra-Lozano J, Fonseca AM, Hatfield J, Kapur P, Gomez AM, Jafri HS, Ramilo O (2004) Anti-respiratory syncytial virus (RSV) neutralizing antibody decreases lung inflammation, airway obstruction, and airway hyper-responsiveness in a murine RSV model. Antimicrob Agents Chemother 48:1811–1822
Mencacci A, Bacci A, Cenci E, Montagnoli C, Fiorucci S, Casagrande A et al (2000a) Interleukin 18 restores defective Th1 immunity to Candida albicans in caspase 1-deficient mice. Infect Immun 68:5126–5131
Mencacci A, Cenci E, Bacci A, Montagnoli C, Bistoni F, Romani L (2000b) Cytokines in candidiasis and aspergillosis. Curr Pharm Biotech 1:235–251
Mencacci A, Cenci BA, Bistoni F, Romani L (2000c) Host immune reactivity determines the efficacy of combination immunotherapy and antifungal chemotherapy in candidiasis. J Infect Dis 181:686–694
Montagnoli C, Bacci A, Bozza S, Gaziano R, Mosci P, Sharpe AH, Romani L (2002) B7/CD28-dependent CD4+CD25+ regulatory T cells are essential components of the memory-protective immunity to Candida albicans. J Immunol 169:6298–6308
Mukherjee J, Scharff MD, Casadevall A (1994) Cryptococcus neoformans infection can elicit protective antibodies in mice. Can J Microbiol 40:888–892
Mukherjee J, Feldmesser M, Scharff MD, Casadevall A (1995) Monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan enhance fluconazole efficacy. Antimicrob Agents Chemother 39:1398–1405
Musso T, Calosso L, Zucca M, Millesimo M, Puliti M, Bulfone-Paus S, Merlino C et al (1998) Interleukin-15 activates proinflammatory and antimicrobial functions in polymorphonuclear cells. Infect Immun 66:2640–2647
Najjar VA (1981) Biochemical aspects of tuftsin deficiency syndrome. Med Biol 59:134–138
Nassar F, Brummer E, Stevens DA (1995) Different components in human serum inhibit multiplication of Cryptococcus neoformans and enhance fluconazole activity. Antimicrob Agents Chemother 39:2490–2493
Natarajan U, Brummer E, Stevens DA (1997) Effect of granulocyte colony-stimulating factor on the candidacidal activity of polymorphonuclear neutrophils and their collaboration with fluconazole. Antimicrob Agents Chemother 41:1575–1578
Nemunaitis J (1998) Use of macrophage colony-stimulating factor in the treatment of fungal infections. Clin Infect Dis 26:1279–1281
Netea MG, Kullberg BJ, Van der Meer JW (2004) Proinflammatory cytokines in the treatment of bacterial and fungal infections. BioDrugs 18:9–22
Nooney L, Matthews RC, Burnie JP (2005) Evaluation of Mycograb(R), amphotericin B, caspofungin, and fluconazole in combination against Cryptococcus neoformans by checkerboard and time-kill methodologies. Diagn Microbiol Infect Dis 51:19–29
Ortoneda M, Capilla J, Pujol I, Pastor FJ, Mayayo E, Fernandez-Ballart J, Guarro J (2002) Liposomal amphotericin B and granulocyte colony-stimulating factor therapy in a murine model of invasive infection by Scedosporium prolificans. J Antimicrob Chemother 49:525–529
Owais M, Ahmed I, Krishnakumar B, Jain RK, Bachhawat BK, Gupta CM (1993) Tuftsin-bearing liposomes as drug vehicles in the treatment of experimental aspergillosis. FEBS Lett 326:56–58
Owais M, Misra-Bhattacharya S, Haq W, Gupta CM (2003) Immunomodulator tuftsin augments antifilarial activity of diethylcarbamazine against experimental brugian filariasis. J Drug Target 11:247–251
Pachl J, Svoboda P, Jacobs F, Vandewoude K, van der HB, Spronk P, Masterson G, Malbrain M, Aoun M, Garbino J et al (2006) A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin Infect Dis 42:1404–1413
Pagano L, Girmenia C, Mele L, Ricci P, Tosti ME, Nosari A, Buelli M et al (2001) Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program. Haematologica 86:862–870
Pappas PG, Perfect JR, Cloud GA, Larsen RA, Pankey GA, Lancaster DJ et al (2001) Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis 33:690–699
Pappas PG, Bustamante B, Ticona E, Hamill RJ, Johnson PC, Reboli A, Aberg J, Hasbun R, Hsu HH (2004) Recombinant interferon gamma 1b as adjunctive therapy for AIDS-related acute cryptococcal meningitis. J Infect Dis 189:2185–2191
Perfect JR, Schell WA (1996) The new fungal opportunists are coming. Clin Infect Dis 22(Suppl 2):S112–S118
Pina A, Valente-Ferreira RC, Molinari-Madlum EE, Vaz CA, Keller AC, Calich VL (2004) Absence of interleukin-4 determines less severe pulmonary paracoccidioidomycosis associated with impaired Th2 response. Infect Immun 72:2369–2378
Pinner RW, Teutsch SM, Simonsen L, Klug LA, Graber JM, Clarke MJ, Berkelman RL (1996) Trends in infectious diseases mortality in the Unites States. JAMA 275:189–193
Pirofski L, Casadevall A (2006) Immunomodulators as an antimicrobial tool. Curr Opin Microbiol 9:489–495
Pugh N, Ross SA, ElSohly MA, Pasco DS (2001) Characterisation of aloeride, a new high-molecular- weight polysaccharide from Aloe vera with potent immunostimulatory activity. J Agric Food Chem 49:1030–1034
Pursell K, Verral S, Daraiesh F, Shrestha N, Skariah A, Hasan E, Pitrak D (2003) Impaired phagocyte respiratory burst responses to opportunistic fungal pathogens in transplant recipients: in vitro effect of r-metHuG-CSF (Filgrastim). Transplant Infect Dis 5:29–37
Ramos RA, De la Torre RA, Alonso N, Villaescusa A, Betancourt J, Vizoso AJ (1996) Screening of medicinal plants for induction of somatic segregation activity in Aspergillus nidulans. J Ethnopharmacol 52:123–127
Revankar SG, Patterson JE, Sutton DA, Pullen R, Rinaldi MG (2002) Disseminated phaeohyphomycosis: review of an emerging mycosis. Clin Infect Dis 34:467–476
Rippon JW (1988) Pseudallescheriasis. In: Rippon JW (ed) Medical mycology, 3rd edn. WB Saunders Company, Philadelphia, pp 651–680
Roilides E, Pizzo PA (1992) Modulation of host defence by cytokines: Evolving adjuncts in prevention and treatment of serious infections in immunocompromised hosts. Clin Infect Dis 15:508–524
Roilides E, Walsh T (2004) Recombinant cytokines in augmentation and immunomodulation of host defenses against Candida spp. Med Mycol 42:1–13
Roilides E, Uhlig K, Venzon D, Pizzo PA, Walsh TJ (1993) Enhancement of oxidative response and damage caused by human neutrophils to Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon. Infect Immun 61:1185–1193
Roilides E, Holmes A, Blake C, Pizzo PA, Walsh TJ (1995a) Effects of granulocyte colony-stimulating factor and interferon-gamma on antifungal activity of human polymorphonuclear neutrophils against pseudohyphae of different medically important Candida species. J Leukoc Biol 57:651–656
Roilides E, Sein T, Holmes A, Chanock S, Blake C, Pizzo PA, Walsh TJ (1995b) Effects of macrophage colony-stimulating factor on antifungal activity of mononuclear phagocytes against Aspergillus fumigatus. J Infect Dis 172:1028–1034
Roilides E, Kadiltsoglou I, Dimitriadou A, Hatzistilianou M, Manitsa A, Karpouzas J, Pizzo PA, Walsh TJ (1997) Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia. FEMS Immunol Med Microbiol 19:169–180
Roilides E, Dignani MC, Anaissie EJ et al (1998a) The role of immunoreconstitution in the management of refractory opportunistic fungal infections. Med Mycol 36(Suppl 1):12–25
Roilides E, Sein T, Schaufele R, Chanock SJ, Walsh TJ (1998b) Increased serum concentrations of interleukin-10 in patients with hepatosplenic candidiasis. J Infect Dis 178:589–592
Roilides E, Dimitriadou-Georgiadou A, Sein T, Kadiltsoglou I, Walsh TJ (1998c) Tumor necrosis factor alpha enhances antifungal activities of polymorphonuclear and mononuclear phagocytes against Aspergillus fumigatus. Infect Immun 66:5999–6003
Roilides E, Maloukou A, Gil-Lamaignere C, Winn RM, Panteliadis C, Walsh TJ (2001) Differential effects of interleukin 15 on hyphal damage of filamentous fungi induced by human neutrophils. Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago. Abstract J-468
Roilides E, Lyman CA, Filioti J, Akpogheneta O, Sein T, Lamaignere CG, Petraitiene R, Walsh TJ (2002) Amphotericin B formulations exert additive antifungal activity in combination with pulmonary alveolar macrophages and polymorphonuclear leukocytes against Aspergillus fumigatus. Antimicrob Agents Chemother 46:1974–1976
Romani L, Mencacci A, Tonnetti L, Spaccapelo R, Cenci E, Puccetti P, Wolf SF, Bistoni F (1994) IL-12 is both required and prognostic in vivo for T helper type 1 differentiation in murine candidiasis. J Immunol 153:5167–5175
Romani L, Puccetti P, Bistoni F (1997) Interleukin-12 in infectious diseases. Clin Microbiol Rev 10:611–636
Sang BH, Young HK, Chang WL, Sun MP, Hae YL, Kyung SA, Ik HK, Hwan MK (1998) Characteristic immunostimulation by angelan isolated from Angelica gigas. Nakai Immunopharm 40(1):39–48
Sasaki E, Tashiro T, Kuroki M, Seki M, Miyazaki Y, Maesaki S et al (2000) Effects of macrophage colony-stimulating factor (M-CSF) on anti-fungal activity of mononuclear phagocytes against Trichosporon asahii. Clin Exp Immunol 119:293–298
Saunders Comprehensive Veterinary Dictionary (2007) 3rd edn. Elsevier
Shamim SS, Waseemuddin Ahmed, Iqbal Azhar (2004) Antifungal activity of Allium, Aloe, and Solanum species. Pharmaceutical Biology 42(7):491–498
Sheehan DJ, Hitchcock CA, Sibley CM (1999) Current and emerging azole antifungal agents. Clin Microbial Rev 12:40–79
Shukla PK, Khan ZK, Mathur KB (1992) Immunomodulatory effect of novel peptides against systemic candidiasis in mice. 32nd Annual Conf Assoc Microbiol India, Madurai, India
Siddiqui AA, Brouwer AE, Wuthiekanun V, Jaffar S, Shattock R, Irving D, Sheldon J, Chierakul W, Peacock S, Day N et al (2005) IFN gamma at the site of infection determines rate of clearance of infection in cryptococcal meningitis. J Immunol 174:1746–1750
Singh SP, Chhabra R, Srivastava VML (1992) Respiratory burst in peritoneal exudate cells in response to a modified tuftsin. Experientia 48:994–996
Singhal A, Bali A, Jain RK, Gupta CM (1984) Specific interactions of liposomes with PMN leukocytes upon incorporating tuftsin in their bilayers. FEBS Lett 178:109–113
Steinbach WJ, Schell WA, Blankenship JR, Onyewu C, Heitman J, Perfect JR (2004) In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus. Antimicrob Agents Chemother 48:1664–1669
Stevens DL (1996) Immune modulatory effects of antibiotics. Curr Opin Infect Dis 9:165–169
Stevens DA (1998) Combination immunotherapy and antifungal chemotherapy. Clin Infect Dis 26:1266–1269
Stevens DA, Walsh TJ, Bistoni F, Cenci E, Clemons KV, Del Sero G, Fe d’Ostiani C, Kullberg BJ, Mencacci A, Roilides E, Romani L (1998) Cytokines and mycoses. Med Mycol 36(Suppl 1):174–182
Stevens DA, Kullberg BJ, Brummer E, Casadevall A, Netea MG, Sugar AM (2000) Combined treatment: antifungal drugs with antibodies, cytokines or drugs. Med Mycol 38(suppl 1):305–315
Stuyt RJ, Netea MG, Verschueren I, Fantuzzi G, Dinarello CA, Van Der Meer JW, Kullberg BJ (2002) Role of interleukin-18 in host defense against disseminated Candida albicans infection. Infect Immun 70:3284–3286
Stuyt RJ, Netea MG, van Krieken JH, van der Meer JW, Kullberg BJ (2004) Recombinant interleukin-18 protects against disseminated Candida albicans infection in mice. J Infect Dis 189:1524–1527
Tan BKH, Vanitha J (2004) Immunomodulatory and antimicrobial effects of some traditional Chinese medicinal herbs: a review. Curr Med Chem 11:1423–1430
Ter MJ, van den Brink EN, Poon LL, Marissen WE, Leung CS, Cox F, Cheung CY, Bakker AQ, Bogaards JA, van DE et al (2006) Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med 3:e237
Tonnetti L, Spaccapelo R, Cenci E, Mencacci A, Puccetti P, Coffman RL, Bistoni F, Romani L (1995) Interleukin-4 and -10 exacerbate candidiasis in mice. Eur J Immunol 25:1559–1565
Tran P, Ahmad R, Xu J, Ahmad A, Menezes J (2003) Host’s innate immune response to fungal and bacterial agents in vitro: up-regulation of interleukin-15 gene expression resulting in enhanced natural killer cell activity. Immunology 10:9263–9270
Vazquez N, Walsh TJ, Friedman D, Chanock SJ, Lyman CA (1998) Interleukin-15 augments superoxide production and microbicidal activity of human monocytes against Candida albicans. Infect Immun 66:145–150
Vazquez-Torres A, Jones-Carson J, Wagner RD, Warner T, Balish E (1999) Early resistance of interleukin-10 knockout mice to acute systemic candidiasis. Infect Immun 67:670–674
Viscoli C, Girmenia C, Marinus A, Collette L, Martino P, Vandercam B, Doyen C, Lebeau B, Spence D, Krcmery V, De Pauw B, Meunier F (1999) Candidemia in cancer patients: a prospective, multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin Infect Dis 28:1071–1079
Vogler BK, Ernst E (1999) Aloe vera: a systematic review of its clinical effectiveness. Br J Gen Prac 49:823–828
Vora S, Chauhan S, Brummer E, Stevens DA (1998a) Activity of voriconazole combined with neutrophils or monocytes against Aspergillus fumigatus: effects of granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor. Antimicrob Agents Chemother 42:2299–2303
Vora S, Purimetla N, Brummer E, Stevens DA (1998b) Activity of voriconazole, a new triazole, combined with neutrophils or monocytes against Candida albicans: effect of granulocyte colony-stimulating factor and granulocyte–macrophage colony-stimulating factor. Antimicrob Agents Chemother 42:907–910
Willment JA, Lin HH, Reid DM, Taylor PR, Williams DL, Wong SY, Gordon S, Brown GD (2003) Dectin-1 expression and function are enhanced on alternatively activated and GM-CSF-treated macrophages and are negatively regulated by IL-10, dexamethasone, and lipopolysaccharide. J Immunol 171:4569–4573
Winn RM, Gil-Lamaignere C, Roilides E, Simitsopoulou M, Lyman CA, Maloukou A, Walsh TJ (2003) Selective effects of interleukin (IL)-15 on antifungal activity and IL-8 release by polymorphonuclear leukocytes in response to hyphae of Aspergillus species. J Infect Dis 188:585–590
Yamaguchi H, Abe S, Tokuda Y (1993) Immunomodulating activity of antifungal drugs. Ann N Y Acad Sci 685:447–457
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Zia, Q. et al. (2010). Immunomodulators: Potential in Treatment of Systemic Fungal Infections. In: Ahmad, I., Owais, M., Shahid, M., Aqil, F. (eds) Combating Fungal Infections. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-12173-9_17
Download citation
DOI: https://doi.org/10.1007/978-3-642-12173-9_17
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-12172-2
Online ISBN: 978-3-642-12173-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)