Modulations of histamine release from mast cells by interleukin-2 is affected by nedocromil sodium.
We have previously demonstrated that histamine release from immunologically activated mast cells (MC) is enhanced by their preincubation (1 h) with interleukin-2(IL-2), and that IL-2 induces slow-chronic histamine release by MC in long-term cultures (6 days). In the present study we assessed whether nedocromil sodium can interfere with IL-2 modulation of MC histamine release. IL-2 enhancing effects nedocromil sodium activity were studied in cocultures of rat peritoneal MC with 3T3 fibroblasts (MC/3T3). MC/3T3 were preincubated for 1 h with IL-2 (50 micrograms/ml) and activated with either rabbit anti-rat IgE or compound 48/80. In chronic experiments MC/3T3 were long-term (5-6 days) incubated with IL-2 (50 micrograms/ml). Nedocromil sodium was used at 10(-5) M. MC activation both when added during the preincubation period (no tachyphylaxis was present) and when added together with the MC activators (30-50% inhibition). Washing out IL-2 before addition of the anti-IgE antibodies did not affect its histamine-release enhancing activity. Removal of nedocromil sodium before addition of the stimulus completely abrogated its effect. Continuous presence of IL-2 in the culture medium enhanced spontaneous histamine release by 37% and this effect was completely abolished in the presence of nedocromil sodium. Furthermore, nedocromil sodium decreased MC basal histamine release by 23% in long-term cocultures. Since IL-2 is known to be elevated in some pathological conditions, our results show that nedocromil sodium inhibits MC activation in an in vitro system which may represent a close resemblance to the in vivo allergic response.
Rubinchik
E
E
Department of Pharmacology, School of Pharmacy, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Norris
A
A
Levi-Schaffer
F
F
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D018920:Coculture Techniques; D006636:Histamine Release / Q000187:drug effects*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D017835:Nedocromil / Q000494:pharmacology*; D051381:Rats; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D018926:Anti-Allergic Agents; D007376:Interleukin-2; D017835:Nedocromil; D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine