Background: Granulocyte macrophage-colony stimulating factor (GM-CSF) has been implicated in the pathogenesis of a number of inflammatory diseases and in osteoarthritis (OA). We identified previously a new GM-CSF→Jmjd3→interferon regulatory factor 4 (IRF4)→chemokine (c-c motif) ligand 17 (CCL17) pathway, which is important for the development of inflammatory arthritis pain and disease. Tumour necrosis factor (TNF) can also be linked with this pathway. Here we investigated the involvement of the pathway in OA pain and disease development using the GM-CSF-dependent collagenase-induced OA (CiOA) model. Methods: CiOA was induced in C57BL/6 wild-type (WT), Irf4 −/− , Ccl17 E/E , Ccr4 −/− , Tnf −/− and GM-CSF −/− mice. Additionally, therapeutic targeting of CCL17, Jmjd3 and cyclooxygenase 2 (COX-2) was evaluated. Development of pain (assessment of weight distribution) and OA disease (histologic scoring of synovitis, cartilage destruction and osteophyte size) were assessed. Synovial joint cells, including neutrophils, macrophages, fibroblasts and endothelial cells, were isolated (cell sorting) and gene expression analyzed (quantitative PCR). Results: Studies in the gene-deficient mice indicated that IRF4, CCL17 and the CCL17 receptor, CCR4, but not TNF, were required for CiOA pain and optimal cartilage destruction and osteophyte size. Therapeutic neutralization of CCL17 and Jmjd3 ameliorated both pain and disease, whereas the COX-2 inhibitor only ameliorated pain. In the synovium Ccl17 mRNA was expressed only in the macrophages in a GM-CSF-dependent and IRF4-dependent manner. Conclusions: The GM-CSF→Jmjd3→IRF4→CCL17 pathway is important for the development of CiOA, with CCL17 thus being a potential therapeutic target for the treatment of both OA pain and disease.

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Acne vulgaris is a disease of pilosebaceous units which results from the interplay between multiple factors. The sequence of events in acne pathogenesis is still not certain, but inflammation is strongly proposed as the early initial factor. 1Propionibacterium acnes initiates and maintains the inflammatory process via different mechanisms including increasing the proinflammatory cytokines mainly interleukin-1beta (IL-1β) release. 2Interleukin-1β can be released from keratinocytes, fibroblasts, and immune cells such as macrophages and mast cells. It can be involved in the etiopathogenesis of inflammatory and autoimmune disorders, as it has a regulatory effect on chemokine expression and T-cell extravasation. Moreover, it is directly implicated in tissue destruction. 3,4 C-reactive protein (CRP), one of the acute phase proteins, is the best indicator of systemic inflammation, as its level elevates rapidly in cases of inflammation, and its serum levels show no circadian changes across the day. IL-1, IL-6 and tumor necrosis factor alpha (TNFα) that are implicated in the pathogenesis of acne are also major inducers of CRP production by the liver. Thus, CRP levels could be elevated in acne if the amount of inflammation is high enough. 5 Recently, the possible value of saliva to monitor the overall health, to diagnose various oral or systemic disorders, 6 and to monitor the therapeutic levels of different drugs to modify and individualize the

IL-1A (-889) gene polymorphism has a role in the pathogenesis of acne vulgaris. We suggest that the triggering or exacerbating effect of diet on acne may be related to IL-1A (-889) gene polymorphism.

Background: Interleukin-15 (IL-15) is a cytokine that is involved in many inflammatory and autoimmune diseases. Although alopecia areata (AA) is an autoimmune disease, serum levels of IL-15 have not been studied well in AA patients. Aim of the Work: We aims at evaluating the serum levels of IL-15 in active AA. Subject and Methods: This case-control study included 40 AA patients and 40 apparently healthy matched controls. Written informed consents were obtained from all the participants. The scalp was examined to assess sites, number, and size of alopecia patches, and the severity of AA lesions was assessed using the Severity of Alopecia Tool score (SALT score) which determine the percentage of hair loss in the scalp. The body was carefully examined to detect any alopecia patches in any hairy area. Nail examination was carried out to detect any nail involvement. Serum IL-15 levels were measured using an ELISA kits. Results: Serum levels of IL-15 in patients were significantly higher than those in the control group ( P < 0.001). Serum levels in alopecia totalis were significantly higher than those with one or two patches, and serum levels in patients with both scalp and body involvement were significantly elevated than the levels of patients with either scalp or body involvement. There was a statistically significant positive correlation between SALT score and serum levels of IL-15 ( P < 0.001). Conclusion: Serum IL-15 may be a marker of AA severity.