Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis.

Abstract

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.

• Authors: K B Madden, J F Urban Jr, H J Ziltener, J W Schrader, F D Finkelman, I M Katona
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 147 Issue 4 Pg. 1387-91 (Aug 15 1991) ISSN: 0022-1767 [Print] United States
• PMID: 1869831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Interleukin-3
• Interleukin-4
• Immunoglobulin E

Topics

• Animals
• Antibodies, Monoclonal (immunology)
• Female
• Immunoglobulin E (biosynthesis)
• Interleukin-3 (physiology)
• Interleukin-4 (physiology)
• Intestinal Diseases, Parasitic (complications, immunology)
• Mast Cells (immunology)
• Mastocytosis (prevention & control)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Nematode Infections (complications, immunology)
• Nippostrongylus