Allergic contact dermatitis (ACD) is a T cell-mediated inflammatory condition. It is marked by erythema, vesiculation, and pruritus. Mast cells (MCs) have a key role to play in the pathogenesis of ACD.

Interleukin-37 (IL-37) is known to relieve inflammatory responses in various allergic diseases. A study was designed to determine the immunomodulatory effect of IL-37 on allergic inflammation. Investigators employed a 2,4-dinitrofluorobenzene (DNFB)-induced ACD experimental model and isolated peritoneal mast cells (RPMCs).

It was noted that systematic application of IL-37 led to a significant relief in ear swelling, reduced inflammatory cell infiltration, diminished inflammatory cytokine production (TNF-α, IL-1β, IFN-γ, and IL-13), resulted in the inhibition of MC recruitment, decreased IgE levels, and reduced IL-33 production in the local ear tissues with DNFB challenge. With IL-37 intervention, RPMCs obtained from ACD models exhibited downregulation of IL-6, TNF-α, IL-13, and MCP-1 production following IL-33 stimulation. They also exhibited β-hexosaminidase reduction and histamine release under DNP-IgE/HSA treatment.

Treatment with IL-37 significantly restricted the NF-κB activation and P38 phosphorylation in ACD RPMCs. SIS3, a specific Smad3 inhibitor, was shown to abrogate the suppressive effects of IL-37 on MC-mediated allergic inflammation, thus pointing to the involvement of Smad3 in the anti-ACD effect of IL-37.

The study thus revealed that IL-37 has a protective action against IL-33-regulated MC inflammatory responses by inhibiting NF-κB and P38 MAPK activation associated wuth the regulation of Smad3 in experimental models with ACD.

Source: Li W, Ding F, Zhai Y, et al. IL-37 is protective in allergic contact dermatitis through mast cell inhibition. Int Immunopharmacol. 2020 Apr 8;83:106476.