title: The roles of interleukins in the synergistic effect of B-cell mitogens with concanavalin A on hydrocortisone-resistant thymic cell proliferation.
abstract: Investigations were made to determine the roles of interleukin (IL)-1 and IL-2 in the synergistic enhancement of DNA synthesis by concanavalin A (Con A) and bacterial lipopolysaccharide (LPS) or butanol-extracted water-soluble adjuvant (Bu-WSA) from Bacterionema matruchotii in cultures of thymic cells taken from hydrocortisone (HC)-treated C3H/HeN (LPS-responsive) and C3H/HeJ (LPS-non-responsive) mice. When the C3H/HeNCrj cells were cultured in the presence of Con A and LPS or Bu-WSA together, [3H]thymidine [( 3H]TdR) uptake of the cells was enhanced synergistically in comparison with those cultured with either one of the mitogens alone. The synergistic effect on thymic cells was dependent on Ia-positive accessory cells, since a previous treatment of the cells with anti-Iak serum and complement inhibited the response, and the inhibition could be relieved by the addition of either purified peritoneal exudate macrophages (Mø) or splenic B lymphocytes. The co-stimulation of cells with Con A and LPS or Bu-WSA also enhanced their production and release of thymic cell growth factor(s) into the culture medium. The amounts of IL-1 and IL-2 in the culture supernatants were sufficiently high to explain the activities of the growth factor(s). On the other hand, enhanced IL-2 production without significant increase in IL-1 was seen in the co-cultures of anti-Ia+ cell deprived thymic cells and purified splenic B cells prepared from C3H/HeNCrj mice in the presence of Con A and LPS or Bu-WSA, and it was seen in the cultures of C3H/HeJ thymic cells with Con A and LPS. These results suggest that the synergistic effect of Con A and LPS or Bu-WSA on the proliferative response of HC-treated thymic cells is mainly due to the enhanced production of IL-2 and its action to increase cell growth, and there are two pathways by which the enhancement of IL-2 production by Con A and LPS or Bu-WSA can occur: an IL-1-dependent pathway, or an IL-1-independent one.
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D004357:Drug Synergism; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006854:Hydrocortisone / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008938:Mitosis / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D008070:Lipopolysaccharides; D003208:Concanavalin A; D004247:DNA; D006854:Hydrocortisone