Interleukin 31 (IL-31) is a four-helix cytokine made predominantly by Th2 CD4+ T cells. It was initially identified as being associated with the promotion of atopic dermatitis, where increased levels of IL-31 levels have been found and IL-31 induced the expression of proinflammatory cytokines and chemokines in a human bronchial epithelial cell line. However, subsequent study has shown that IL-31RA knockout mice developed exacerbated type 2 inflammation in the lung following infection with Schistosoma mansoni eggs. In this study, we investigated the dynamic expression of IL-31 and IL-31RA during eight consecutive ovalbumin (OVA) challenges and measured the chemokines from lung alveolar epithelial cells induced by IL-31. In addition, we examined the effect deletion of IL-31RA has on lung inflammation and the differentiation of CD4+ T cells. Our results demonstrate that the expression of IL-31 and IL-31RA was elevated after each weekly OVA challenge, although slightly less of both observed after the first week of OVA challenge. IL-31 also promoted the expression of inflammatory chemokines CCL5, CCL6, CCL11, CCL16, CCL22, CCL28, CX3CL1, CXCL3, CXCL14 and CXCL16 in alveolar epithelial cells. Migration of macrophages and T cells was enhanced by culture supernatants of IL-31-stimulated alveolar epithelial cells. Lastly, and in contrast to the IL-31 results, mice deficient in IL-31RA developed exacerbated lung inflammation, increased IL-4-positive cell infiltrates and elevated Th2 cytokine responses in draining lymph nodes. The proliferation of IL-31RA−/− CD4+ T cells was enhanced in vitro after anti-CD3/anti-CD28 antibody stimulation. These data indicate that IL-31/IL-31RA may play dual roles, first as an early inflammatory mediator promoting the secretion of chemokines to recruit inflammatory cells, and subsequently as a late inflammatory suppressor, limiting Th2 cytokine responses in allergic asthma.

Several different vaccines have been produced for human use to prevent the highly pathogenic H5N1 influenza. Some studies reported that the clinical effectiveness of influenza vaccines in older adults may be lower than in younger adults. In this study, a meta-analysis of the immunogenicity of H5N1 influenza vaccines in elderly adults was performed. Database search was conducted in EMBASE, PubMed, the Cochrane Library, Chinese VIP, Wanfang and CBM. A total of 3951 elderly adults from 10 articles were included in the meta-analysis. Compared to a single dose, two doses of H5N1 vaccines resulted in the higher seroconversion and seroprotection. For all groups treated with adjuvanted vaccines, there were significant increases (1.55- to 2.16-fold) in the seroconversion rates (SCRs) and seroprotection rates (SPRs) after two immunizations. Oil-in-water emulsion (OE)-adjuvanted 7.5 μg vaccine caused higher antibody responses than 3.75 μg of vaccine (SCR: risk ratio (RR) = 1.26 (1.19, 1.33); SPR: RR = 1.25 (1.14, 1.36)). Elderly adults exhibited slightly lower antibody responses only when given 7.5 μg of OE-adjuvanted vaccine (SCR: RR = 1.06 (1.01, 1.11)) than younger adults. After treatment with the 7.5 μg of OE-adjuvanted vaccines, the most commonly reported adverse events were injection site pain, swelling and erythema, with the incidence of 32%, 3% and 2%, respectively, and no serious adverse events were found. These data demonstrate that two doses of 7.5 µg of OE-adjuvanted H5N1 vaccine are well tolerated and induce a robust antibody response in elderly adults.

Inoculation with vaccine is the major intervention currently used to prevent influenza infections. However, it will be a challenge to produce and implement a new vaccine when a novel highly pathogenic influenza virus emerges in humans as significant infections. H7 subtype influenza viruses have similar epitopes on hemagglutinin, which can induce cross-reactive antibodies. In this study, a meta-analysis of the cross-reactivity of antibodies induced by one H7 subtype influenza vaccine against other H7 subtypes was performed. Database search was conducted in PubMed, Cochrane Library, EMBASE, MEDLINE, Chinese Biological Medicine Database (CBM), and Wanfang. A total of 9 articles comprising 811 human subjects were included in this meta-analysis. All assessed H7 influenza vaccines induced vaccine strain-specific protective antibodies [seroconversion rate (SCR) = 0.74, 95% CI (0.65, 0.82); seroprotection rate (SPR) = 0.81, 95% CI (0.78, 0.83)]. All H7 influenza virus monovalent vaccines exhibited cross-reactivity tested by hemagglutinin inhibition test (HI), microneutralization test (MN) and immunosorbent assay (ELISA) to other H7 subtype viruses. H7N1, H7N3, H7N7, and H7N9 vaccines elicited cross-reactive antibodies against other H7 subtype influenza viruses [SCR = 0.66, 95% CI (0.50, 0.82); SPR = 0.79, 95% CI (0.67, 0.91)]. The pooled SCR (95%CI) of cross-reactivity of H7N1 and H7N3 vaccines were 0.88 (0.85, 0.91) and 0.40 (0.26, 0.54), respectively. The consolidated SPR (95%CI) of H7N1 and H7N7 vaccines were 0.89 (0.86, 0.92) and 0.93 (0.81, 1.06). All H7 vaccines induced crossreactive antibodies against H7N9 viruses [SCR = 0.69, 95% CI (0.52, 0.86); SPR = 0.85, 95% CI (0.76, 0.94)]. H7 vaccines can be used to limit influenza infection when a new highly pathogenic H7 virus appears.