Interleukin-16 inhibits interleukin-13 production by allergen-stimulated blood mononuclear cells.
Expression of interleukin (IL)-16 is increased in bronchial mucosal biopsies of atopic asthmatics compared to normal controls. The functional significance of increased expression of IL-16 at sites of allergic inflammation is not yet clear. We have previously shown that IL-16 inhibits IL-5 secretion by allergen-stimulated peripheral blood mononuclear cells (PBMC). We investigated whether IL-16 inhibits the production of other T helper 2 cytokines, namely IL-13 and IL-4, by allergen-specific T cells. PBMC from ragweed-sensitive atopic subjects were stimulated with allergen extract for cytokine production in the presence or absence of rhIL-16. Production of cytokines was assessed by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. To evaluate whether the modulatory effect of IL-16 on cytokine synthesis was mediated by interferon-gamma (IFN-gamma), IL-10, IL-12 or IL-18, allergen-stimulated PBMC were cultured in presence of IL-16 and neutralizing concentrations of relevant antibodies. Allergen-stimulated PBMC produced significantly elevated levels of IL-13 (90-740 pg/ml) as compared to unstimulated PBMC (0-375 pg/ml, P < 0.01). Addition of rhIL-16 resulted in down-regulation of IL-13 mRNA expression as well as significantly reduced amounts of IL-13 released by allergen-stimulated PBMC (0-457 pg/ml, P < 0.001), as observed for IL-5. No effect of IL-16 was observed on IL-4 mRNA expression. Treatment with IL-16 resulted in increased levels of IL-10 and IL-18 in allergen-stimulated cell culture. Neutralization of IFN-gamma, IL-12, IL-10 or IL-18 did not alter the inhibitory effects of IL-16 on IL-13 and IL-5 secretion by allergen-stimulated PBMC. IL-16 did not modify IL-13 synthesis by anti-CD3-stimulated CD4(+) T cells, but it significantly reduced the production of IL-5. These data suggest that IL-16 may play an important immunoregulatory role in allergic states in response to allergen.
El Bassam
Souad
S
Laboratory of Immunology, Research Center, Ste-Justine Hospital, University of Montreal, Canada.
Pinsonneault
Stéphane
S
Kornfeld
Hardy
H
Ren
Fucheng
F
Menezes
José
J
Laberge
Sophie
S
D000485:Allergens / Q000276:immunology*; D031164:Ambrosia / Q000276:immunology; D001249:Asthma / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000235:genetics; D019410:Interleukin-16 / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D011058:Pollen / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology
D000485:Allergens; D018793:Interleukin-13; D019410:Interleukin-16; D015848:Interleukin-5; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4