IL-4 influences IL-2 production and granulomatous inflammation in murine schistosomiasis mansoni.
In previous studies the dynamics of IL-2 production by splenic cells of Schistosoma mansoni infected mice was correlated with the intensity of hepatic granulomatous inflammation. To extend those observations, the present studies examined the role of IL-4 on the immune responsiveness of infected mice. The dynamics of IL-4 production by soluble egg Ag-stimulated splenic cells was similar to that of IL-2: minimal levels at the pre-oviposition or early worm egg deposition stages (4 to 6 wk) peak production coincident with maximal granulomatous response (8 wk) followed by a concurrent decline at the chronic stage (18 to 20 wk) in both parameters. Addition of murine rIL-4 to splenocyte cultures of acutely or chronically infected mice did not significantly enhance the soluble egg Ag-elicited proliferative response. Daily injections of rIL-4 (10 to 1000 U) given for 14 days to groups of mice with acute infection, at the high dose-enhanced IL-2, but not IL-4, production. Similar treatment given to chronically infected mice did not augment diminished lymphokine production. Chronically infected mice treated with 10 to 1000 U of rIL-4 showed significantly enhanced liver granulomatous responses compared with untreated animals and the augmented granulomas contained more enlarged macrophages and connective tissue matrix. Repeated injections of anti-IL-4 mAb (11B11) given to acutely infected mice significantly suppressed splenic cell proliferation, IL-2 and IL-4 production, and hepatic granulomatous inflammation. Similar treatment given to chronically infected mice also diminished the down-modulated granulomatous response. These data demonstrate that IL-4 plays an important role in the egg-directed granulomatous response and participates in the regulation of Ag-specific lymphoproliferation, and IL-2 and IL-4 production during the course of the infection.
Yamashita
T
T
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201.
Boros
D L
DL
D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D006099:Granuloma / Q000276:immunology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins / Q000494:pharmacology; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4