Is it Beneficial to Augment or to Inhibit Neutrophil Function in Severe Infections and Sepsis?
The neutrophil plays a key role in host defense against microbial infections. Neutrophils move to sites of infection in response to chemotactic substances generated by infectious agents. At the site of infection, the neutrophils identify and engulf invading agents through specific cell surface receptors. A complex array of oxidative and non-oxidative mechanisms present in the neutrophil then kills invading microorganisms . Reductions in neutrophil count or functions predispose the host to infections. For example, regular reductions in neutrophil numbers, which occurs in a rare human disease (cyclic neutropenia), predispose the inflicted individuals to recurring symptoms of infectious disease [2, 3]. Furthermore, in patients undergoing chemotherapy, incidence and prevalence of infections decrease with increasing numbers of neutrophils . Functional abnormalities of neutrophils may also mean a predisposition to infections. Functional failure of neutrophils occurs in chronic granulomatous disease. Neutrophils of patients with this inherited disease lack the capacity to have a respiratory burst. Since the respiratory burst is essential in phagocytic killing of microorganisms, patients with this disease have recurrent bouts of serious infections despite normal neutrophil counts .
KeywordsBacterial Meningitis Respiratory Burst Chronic Granulomatous Disease Neutrophil Function Cyclic Neutropenia
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- 2.Dale DC (1991) Leucocytosis, leukopenia, and eosinophilia. In: Wilson JD, Braunwald E, Isselbacher KJ, et al (eds) Harrison’s principles of internal medicine. McGraw-Hill, New York, pp 359–362Google Scholar
- 8.Pascual C, Oberhoffer M, Königs D, et al (1996) Leukocyte activation during sepsis. Clin Intensive Care 7: P8 (Abst)Google Scholar
- 27.Dale DC, Liles WC, Summer WR, Nelson S (1995) Review: Granulocyte, colony-stimulating factor: Role and relationships in infectious diseases. J Infect Dis 172: 1061–1075Google Scholar
- 28.De Haas M, Kerst JM, Van der Schoot E, et al (1994) Granulocyte colony-stimulating factor administration to healthy volunteers: Analysis of the intermediate activating effects on circulating neutrophils. Blood 84: 3885–3894Google Scholar
- 30.Hammond WP, Csiba E, Canin A, et al (1991) Chronic neutropenia. A new canine model induced by human granulocyte colony-stimulating factor. J Clin Invest 87: 704–710Google Scholar
- 32.Bacigalupo A (1994) The clinical benefits of recombinant human granulocyte colony-stimulating factor in the treatment of cancer patients. Eur J Cancer 30A: S26 - S29Google Scholar
- 34.Reinhart K, Wiegend-Löhnert C, Grimminger F, et al and the MAK 195F Sepsis Study Group (1996) Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock: A multicenter, randomized, placebo-controlled, dose-ranging study. Crit Care Med 24: 733–742Google Scholar
- 41.Smith WS, Sumnicht GE, Sharpe RW, Samuelson D, Millard FE (1995) Granulocyte colony-stimulating factor versus placebo in addition to penicillin G in a randomized blinded study of Gram-negative pneumonia sepsis: Analysis of survival and multiorgan failure. Blood 86: 1301–1309Google Scholar
- 42.Karzai W, Natanson C, Patterson M, et al (1994) Effects of a murine monoclonal antibody (MAb) against leukocyte CD1 lb adhesion protein during toxic oxygen exposure in rats. Am J Respir Crit Care Med 149: A430 (Abst)Google Scholar
- 43.Nelson S, Farkas S, Fotheringham N, Ho H, Marrie T, Movahhed H (1996) Filgastrim in the treatment of hospitalized patients with community-acquired pneumonia (CAP). Am J Respir Crit Care Med 149: A535 (Abst)Google Scholar