Modulation by IL-10 of antigen-induced IL-5 generation, and CD4+ T lymphocyte and eosinophil infiltration into the mouse peritoneal cavity.
Sensitized BALB/c mice challenged i.p. with 1 microgram of OVA showed IL-5 release in the peritoneal lavage fluid, which peaked at 6 h and decreased thereafter. This was followed by a massive eosinophil accumulation, which started at 6 h and reached a plateau between 24 and 48 h. The i.p. injection of recombinant murine (rm) IL-10 (0.01-0.1 microgram/cavity) along with OVA reduced IL-5 release at 6 h and allergic eosinophilia at 6, 24, and 48 h. rmIL-10 also blocked in vitro IL-5 generation by sensitized peritoneal cells cultured in the presence of OVA. The inhibitory effect of rmIL-10 on Ag-induced eosinophilia and IL-5 release was suppressed by pretreatment of the animals with 1 mg/mouse of a neutralizing anti-mIL-10 mAb. Flow cytometric analysis revealed an increase in the number of CD4+ and CD8+ T lymphocytes and in the number of CD25+/CD4+ cells in the peritoneal lavage fluid collected 24 and 48 h after challenge, respectively; these numbers were reduced significantly by the administration of 0.1 microgram of rmIL-10. Finally, rmIL-10 failed to modify the anti-CD3-induced IL-5 release in vivo in the peritoneal cavity and in vitro from purified spleen CD4+ T lymphocytes. This suggests that rmIL-10 acts indirectly, by deactivating APC, rather than directly on T cell activation. These findings indicate that rmIL-10 displays anti-allergic activity in sensitized BALB/c mice by preventing Ag-induced CD4+ T lymphocyte and eosinophil accumulation as well as IL-5 release in the peritoneal cavity.
Zuany-Amorim
C
C
Unit of Cellular Pharmacology, Associated Unit of Pasteur Institut/INSERM Unit 285, Paris, France.
Créminon
C
C
Nevers
M C
MC
Nahori
M A
MA
Vargaftig
B B
BB
Pretolani
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000494:pharmacology*; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010529:Peritoneal Cavity / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000941:Antigens; D015848:Interleukin-5; D011994:Recombinant Proteins; D016753:Interleukin-10; D010047:Ovalbumin