Reciprocal immunomodulatory effects of gamma interferon and interleukin-4 on filaria-induced airway hyperresponsiveness.
Tropical pulmonary eosinophilia (TPE) is a severe asthmatic syndrome of lymphatic filariasis, in which an allergic response is induced to microfilariae (Mf) in the lungs. Previously, in a murine model for TPE, we have demonstrated that recombinant interleukin-12 (IL-12) suppresses pulmonary eosinophilia and airway hyperresponsiveness (AHR) by modulating the T helper (Th) response in the lungs from Th2- to Th1-like, with elevated gamma-interferon (IFN-gamma) production and decreased IL-4 and IL-5 production. The present study examined the immunomodulatory roles of IL-4 and IFN-gamma in filaria-induced AHR and pulmonary inflammation using mice genetically deficient in these cytokines. C57BL/6, IL-4 gene knockout (IL-4(-/-)), and IFN-gamma(-/-) mice were first immunized with soluble Brugia malayi antigens and then inoculated intravenously with 200,000 live Mf. Compared with C57BL/6 mice, IL-4(-/-) mice exhibited significantly reduced AHR, whereas IFN-gamma(-/-) mice had increased AHR. Histopathologically, each mouse strain showed increased cellular infiltration into the lung parenchyma and bronchoalveolar space compared with naïve animals. However, consistent with changes in AHR, IL-4(-/-) mice had less inflammation than C57BL/6 mice, whereas IFN-gamma(-/-) mice had exacerbated pulmonary inflammation with the loss of pulmonary architecture. Systemically, IL-4(-/-) mice produced significantly higher IFN-gamma levels compared with C57BL/6 mice, whereas IFN-gamma(-/-) mice produced significantly higher IL-4 levels. These data indicate that IL-4 is required for the induction of filaria-induced AHR, whereas IFN-gamma suppresses AHR.
Mehlotra
R K
RK
Division of Geographic, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Hall
L R
LR
Haxhiu
M A
MA
Pearlman
E
E
D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology*; D017178:Brugia malayi / Q000276:immunology*; D004605:Elephantiasis, Filarial / Q000150:complications / Q000276:immunology*; D005849:Gerbillinae; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011657:Pulmonary Eosinophilia / Q000150:complications / Q000276:immunology*
D015847:Interleukin-4; D007371:Interferon-gamma