Topical applications of an emollient reduce circulating pro-inflammatory cytokine levels in chronically aged humans: a pilot clinical study.

BACKGROUND: While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing-associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimer's disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age-associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels. OBJECTIVE: We performed a pilot study to determine whether improving epidermal function reduces circulating pro-inflammatory cytokine levels in aged humans. METHODS: Thirty-three aged humans were topically treated twice-daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age-related, plasma cytokines (IL-1ß, IL-6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system. RESULTS: We also found significantly higher baseline levels of IL-1ß, IL-6 and TNFα in aged vs. young humans (P < 0.001), as previously reported. Topical applications of the barrier repair emollient significantly enhanced epidermal permeability barrier function (P < 0.01) and stratum corneum hydration (P < 0.05). In parallel, circulating levels of IL-1ß and IL-6 normalized, while TNFα levels declined substantially. CONCLUSION: The results of this preliminary study suggest that a larger clinical trial should be performed to confirm whether improving epidermal function also can reduce circulating pro-inflammatory cytokine levels in aged humans, while also possibly attenuating the downstream development of chronic inflammatory disorders in the aged humans.

CD8α¯ DC is the major DC subset which mediates inhibition of allergic responses by Schistosoma infection.

Our and others' previous studies have shown that Schistosoma japonicum (SJ) infection can inhibit allergic reactions. We recently reported that DCs played an important role in SJ infection-mediated inhibition of allergy, which was associated with enhanced IL-10 and T regulatory cell responses. Here, we further compared the role of CD8α(+) DC and CD8α(-) DC subsets for the inhibitory effect. We sorted CD8α(+) DC (SJCD8α(+) DC) and CD8α(-) DC (SJCD8α(-) DC) from SJ-infected mice and tested their ability to modulate allergic responses in vivo. The data showed that the adoptive transfer of SJCD8α(-) DC was much more efficient than SJCD8α(+) DC for the suppression of allergic airway eosinophilia, mucus overproduction, antigen-specific IgE responses, and Th2 cytokines (IL-4 and IL-5). More importantly, we found that the transfer of SJCD8α(-) DC, but not SJCD8α(+) DC, significantly increased IL-10 and TGF-ß production following OVA exposure. As control, the transfer of DC subsets from naïve mice had no significant effect on allergic inflammation. In addition, SJCD8α-DC expressed significantly higher IL-10 but lower IL-12, CD80 and CD86 than SJCD8α(+) DC, fitting a tolerogenic phenotype. The results suggest that CD8α(-) DC is the predominant DC subset which is involved in the parasitic infection-mediated inhibition of allergic inflammation and possibly through enhancing immunomodulatory cytokine (IL-10 and TGF-ß) production.