Role of gamma interferon in the pathogenesis of severe schistosomiasis in interleukin-4-deficient mice.
In the absence of interleukin-4 (IL-4), infection with Schistosoma mansoni leads to a severe fatal disease rather than the chronic survivable condition that occurs in wild-type (WT) mice. Because the sustained production of NO most closely correlates to weight loss and fatality in infected IL-4(-/-) mice and because gamma interferon (IFN-gamma) is an important inducer of inducible NO synthase, infected IL-4(-/-) mice were treated with anti-IFN-gamma antibodies to determine the role of IFN-gamma during schistosomiasis in WT and IL-4(-/-) animals. When IFN-gamma was neutralized, Th2 responses were enhanced and NO production was reduced in both WT and IL-4(-/-) mice. The decreased NO production correlated with a rescue of proliferation in splenocytes from infected IL-4(-/-) mice. Furthermore, the neutralization of IFN-gamma in vivo improved the gross appearance of the liver and led to a reduction in granuloma size in infected IL-4(-/-) but not WT mice. However, the neutralization of IFN-gamma in vivo did not affect the development of severe disease in infected IL-4(-/-) mice. These results suggest that while the increased production of IFN-gamma does lead to some of the pathology observed in infected IL-4(-/-) mice, it is not ultimately responsible for cachexia and death.
La Flamme
A C
AC
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Patton
E A
EA
Pearce
E J
EJ
D000818:Animals; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D002455:Cell Division; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology*; D015847:Interleukin-4 / Q000172:deficiency* / Q000235:genetics; D008099:Liver / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009500:Neutralization Tests; D009569:Nitric Oxide / Q000096:biosynthesis; D012555:Schistosomiasis mansoni / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells
D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma