Interleukin-16 stimulates the expression and production of pro-inflammatory cytokines by human monocytes

Interleukin-16 (IL-16) acts as a chemoattractant for CD4(+) cells, as a mod ulator of T-cell activation, and plays a key role in asthma. This report de scribes the cytokine-inducing effects of IL-16 on total peripheral blood mo nonuclear cells (PBMC) and PBMC subpopulations. While CD4(+) T lymphocytes did not secrete cytokines in response to rhIL-16, CD14(+) CD4(+) monocytes and maturing macrophages secrete IL-1 beta, IL-6, IL-15 and tumour necrosis factor-alpha (TNF-alpha) upon rhIL-16 stimulation. The mRNA species for th ese four cytokines were detected as early as 4 hr post-stimulation, with pr otein being secreted by 24 hr. Secretion of IL-1 beta and IL-6 by total PBM C was dose dependent, with maximal secretion being observed using 50 ng/ml rhIL-16. However, for IL-15 or TNF-alpha maximal secretion by total PBMC oc curred with all concentrations between 5 ng/ml to 500 ng/ml rhIL-16. Purifi ed monocytes/macrophages secreted maximal concentrations of all four cytoki nes in the presence of 500 ng/ml rhIL-16, except for monocytes where maxima l secretion of IL-15 was, interestingly, observed with only 50 ng/ml rhIL-1 6. The use of higher concentrations of rhIL-16 (1000 ng/ml) inhibited secre tion of all four cytokines. While these IL-16-induced cytokines are likely to be involved in the immune system's response to antigen, the data suggest that IL-16 may play a key role in initiating and/or sustaining an inflamma tory response.