Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis.
Rodents infected with the nematode parasite Nippostrongylus brasiliensis (Nb) develop intestinal mastocytosis, eosinophilia, and elevated serum IgE levels. Although IL-4 and IL-5 are necessary for stimulation of IgE synthesis and eosinophilia, respectively, the cytokines that regulate gut mast cell hyperplasia have not been identified. To address this question, 6- to 8-wk-old BALB/c mice were injected on day 0 and day 7 of Nb infection with a rat anti-mouse IL-4 mAb, and with polyclonal sheep (day 0) and rabbit (day 7) anti-mouse IL-3 IgG antibodies. Additional Nb-infected mice received equal doses of isotype- and species-matched control antibodies. Mice were sacrificed on days 12 or 13 post-infection, and mucosal mast cells (MMC) in sections of the small intestine were enumerated. Nb infection induced a 25- to 40-fold increase in MMC over that observed in uninfected controls. Anti-IL-3 or anti-IL-4 alone suppressed the Nb-induced MMC response by 40 to 50%, whereas both antibodies combined suppressed the MMC response by 85 to 90%. Anti-IL-3 alone had no effect on the serum IgE levels, which were essentially abrogated in the Nb-infected mice treated with anti-IL-4. Blood eosinophilia was not affected by treatment with anti-IL-3 and/or anti-IL-4. These studies demonstrate that IL-3 and IL-4 are physiologically important stimuli of mastocytosis in vivo, and suggest therapeutic interventions that may counteract adverse host responses to allergens as well as to parasites.
Madden
K B
KB
Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Urban
J F
JF
Ziltener
H J
HJ
Schrader
J W
JW
Finkelman
F D
FD
Katona
I M
IM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007377:Interleukin-3 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D007411:Intestinal Diseases, Parasitic / Q000150:complications / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D008415:Mastocytosis / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009349:Nematode Infections / Q000150:complications / Q000276:immunology*; D009559:Nippostrongylus
D000911:Antibodies, Monoclonal; D007377:Interleukin-3; D015847:Interleukin-4; D007073:Immunoglobulin E