A family consisting of at least ten distinct novel 8-10 kd cytokines has been identified over the past 12 years. These cytokines exhibit from 20 to 45% homology in amino acid sequence, are probably all basic heparin-binding polypeptides, and have proinflammatory and reparative activities. The cDNA for these cytokines are characterized by conserved single open reading frames, typical signal sequences in the 5' region, and AT rich sequences in the 3' untranslated regions. Those human cytokines known as interleukin 8, platelet factor 4, beta thromboglobulin, IP-10 and melanoma growth stimulating factor or GRO can be assigned to a subfamily based on their location on chromosome 4 and unique structural features, whereas the second subset consisting of LD78, ACT-2, I-309, RANTES, and macrophage chemotactic and activating factor (MCAF) are all closely linked on human chromosome 17. In this review we have summarized and discussed the available information concerning the regulation and structure of the genes, the structure and biochemical properties of the polypeptide products, their receptors, signal transduction, cell sources, and in vitro as well as in vivo activities of these cytokines.

Use of a humanized anti-interleukin-17 monoclonal antibody, ixekizumab, improved the clinical symptoms of psoriasis. Further studies are needed to establish its long-term safety and efficacy in patients with psoriasis. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT01107457.).

The recognition of the central role of interleukin (IL)-17A in the pathogenesis of psoriasis has led to the development of several monoclonal antibodies targeting this cytokine or its receptors for therapeutic purposes. IL-17A also plays an important role in immunological protection against infections, especially those due to Candida spp., as evidenced by findings in patients with genetic defects in IL-17-related immune responses. To assess the potential of anti-IL-17 treatment to promote Candida infections, here we have systematically reviewed published clinical trials of patients with psoriasis or psoriatic arthritis. Candida infections were reported in 4·0% of patients treated with brodalumab, 1·7% with secukinumab and 3·3% with ixekizumab vs. 0·3%, 2·3% and 0·8% of those assigned to placebo, ustekinumab or etanercept, respectively. Although the incidence of Candida infection was found to be increased by only a small degree during anti-IL-17 therapy, patients undergoing such treatment should be monitored for fungal infection and treated as necessary. We propose adoption of the recently updated recommendations for the practical management of Candida infection in patients administered IL-17 inhibitors.

clinicaltrials.gov Identifier: NCT01137188.