Interleukin-12 suppresses filaria-induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness.
Tropical Pulmonary Eosinophilia (TPE) is a severe form of allergic asthma caused by the host inflammatory response to filarial helminths in the lung microvasculature, and is characterized by pulmonary eosinophilia, increased filarial-specific IgG and IgE antibodies, and airway hyperresponsiveness. The current study examined the effect of IL-12 on pulmonary eosinophilia, deposition of eosinophil major basic protein and airway hyperresponsiveness in mice inoculated i.v. with Brugia malayi microfilariae. Injection of recombinant murine IL-12 modulated the T helper (Th) response in the lungs from Th2- to Th1-like, with elevated IFN-gamma, and decreased IL-4 and IL-5 production. Consistent with this shift in cytokine response, antigen-specific IgG2a was elevated, and IgG1 and total serum IgE were decreased. In addition, eosinophils in BAL fluid from IL-12 treated mice were reduced from 56% to 11%, and there was no detectable MBP on respiratory epithelial cells. Importantly, IL-12 suppressed airway hyperresponsiveness compared with saline-injected control animals. Taken together, these data clearly demonstrate that by modulating Th associated cytokine production, IL-12 down-regulates filaria-induced lung immunopathology.
Mehlotra
R K
RK
Division of Geographic and Pulmonary Medicine, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Hall
L R
LR
Higgins
A W
AW
Dreshaj
I A
IA
Haxhiu
M A
MA
Kazura
J W
JW
Pearlman
E
E
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D017178:Brugia malayi / Q000276:immunology; D002642:Chick Embryo; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000276:immunology*; D005260:Female; D005368:Filariasis / Q000276:immunology*; D005849:Gerbillinae; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008842:Microfilariae / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D013154:Spleen / Q000276:immunology
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D018664:Interleukin-12; D007073:Immunoglobulin E