Role of IL-16 in delayed-type hypersensitivity reaction

Abstract

Interleukin (IL)-16 is a chemoattractant cytokine for CD4+ leukocytes. Because delayed-type hypersensitivity (DTH) reaction is mediated by T helper 1 (Th1) cells and CD4+ T cells can be chemoattracted by IL-16, we have investigated the involvement of IL-16 in the DTH reaction. Immunohistochemical analysis revealed the IL-16 expression in infiltrating cells and epithelial cells in the DTH footpads. The IL-16 expression was also detected intracellularly in the infiltrating cells. In addition, markedly increased production of IL-16 was detected in the DTH footpad extracts, but not in the control footpad extracts, by an enzyme-linked immunosorbent assay and also by Western blot analysis. The DTH footpad extracts exhibited a strong chemoattractant activity toward splenic T cells, which was significantly inhibited by the inclusion of neutralizing monoclonal antibody (mAb) against IL-16 in the migration assay. Furthermore, treatment of sensitized mice in vivo with the anti-IL-16 neutralizing mAb significantly suppressed the footpad swelling induced by an antigen challenge, together with decreased infiltration of leukocytes including not only CD4+ T cells but also CD8+ T cells and macrophages into the DTH footpads. Decreased production of macrophage inflammatory protein 1 was also observed in the DTH footpad extracts by the mAb treatment. These results suggest that IL-16 plays an important role in the recruitment of leukocytes—presumably including antigen-specific Th1 cells, which secrete cytokines and chemokines mediating the following hypersensitivity reaction after activation by the interaction with Langerhans cells carrying the antigen—for the elicitation of DTH response.

The Long‐term Impaired Macrophages Functions are Already Observed Early after High‐dose Ethanol Administration

“…Among other effectors function, macrophages are important to mediate antigen clearance at the site of inflammation and initiate tissue regeneration [24,25]. Our findings demonstrated that high-dose EtOH administration has a drastic impact in imumunogen-driven DTH, reported as impaired OVA clearance in vivo after Figure 3 Long-term impact of high-dose ethanol (EtOH) administration on peritoneal macrophage functional aspects.…”

Immune mechanisms in interstitial lung diseases

“…Some data suggest a role for IL‐16 in the pathogenesis of ILDs. This cytokine, which is involved in the pathogenesis of hypersensitivity reactions ( 101), might direct lymphocyte migration from the circulation into sites of inflammation and tissue injury in ILDs. In fact, IL‐16 shares chemoattractant activity for eosino‐phils and CD4 T cells, and high amounts of IL‐16 have been detected in ILDs, specifically at sites of inflammatory processes, where a perivascular accumu‐lation of lymphocytes may be demonstrated ( 102).…”

Interleukin‐16 aggravates ovalbumin‐induced allergic inflammation by enhancing Th2 and Th17 cytokine production in a mouse model

“…Many studies have shown that the increasing expression of IL-16 has been demonstrated in a variety of diseases, including asthma. 30 Interleukin-16 was previously identified in the BALF 4 hr after antigen challenge in asthmatic subjects. 31 Increased airway expression of IL-16 was detected in bronchial biopsy samples obtained from allergic subjects with asthma 24 hr after allergen challenge.…”