IL-36 receptor antagonistic antibodies inhibit inflammatory responses in preclinical models of psoriasiform dermatitis.

Psoriasis vulgaris (PV) results from activation of IL-23/Th17 immune pathway and is further amplified by cytokines/chemokines from skin cells. Among skin-derived pro-inflammatory cytokines, IL-36 family members are highly upregulated in PV patients and play a critical role in general pustular psoriasis. However, there is limited data showing crosstalk between the IL-23 and IL-36 pathways in PV. Herein, potential attenuation of skin inflammation in the IL-23-induced mouse model of psoriasiform dermatitis by functional inhibition of IL-36 receptor (IL-36R) was interrogated. Anti-mouse IL-36R monoclonal antibodies (mAbs) were generated and validated in vitro by inhibiting IL-36α-induced secretion of CXCL1 from NIH 3T3 cells. Antibody target engagement was demonstrated by inhibition of CXCL1 production in a novel acute model of IL-36α systemic injection in mice. In addition, anti-IL-36R mAbs inhibited tissue inflammation and inflammatory gene expression in an IL-36α ear injection model of psoriasiform dermatitis demonstrating engagement of the target in the ear skin. To elucidate the possible role of IL-36 signalling in IL-23/Th17 pathway, the ability of anti-IL-36R mAbs to inhibit skin inflammation in an IL-23 ear injection model was assessed. Inhibiting the IL-36 pathway resulted in significant attenuation of skin thickening and psoriasis-relevant gene expression. Taken together, these data suggest a role for IL-36 signalling in the IL-23/Th17 signalling axis in PV.

Social and economic factors associated with recent and lifetime incarceration among Puerto Rican drug users.

Using a sample of 280 Puerto Rican drug users with a history of incarceration residing in Massachusetts, we explore whether a significant association exists between social and economic factors (maintaining social network contacts, receiving public assistance) and lifetime incarceration. Analysis of survey data using regression methods shows that respondents who live in their own home, receive public assistance, and have recent familial contact are significantly less likely to have been incarcerated in the past 6 months. Among study participants, men and those who initiated heroin use at younger ages are more likely to have greater lifetime incarceration totals. Practice implications are discussed.

Modifications of evidence-based practices in community-based addiction treatment organizations: a qualitative research study.

This qualitative research effort explored implementation of evidence-based practices (EBPs) in 100 community-based addiction treatment organizations (CBOs) nationwide. The study describes CBO program director attitudes on: (1) satisfaction with EBPs they were mandated to implement; (2) the extent to which their organization modified the EBPs; (3) reasons for modifications; and, (4) the standards they used for modifications. Findings indicate that program directors were highly positive both about EBPs implemented and the modifications made to those EBPs. A broad range of modifications were identified; most common were adding or deleting intervention sessions in efforts to serve the needs of a specific client population. Given the addiction treatment field's lack of standards for modifying EBPs, it is not surprising that little consistency occurred in modification efforts. As government funders of addiction treatments require that CBOs implement EBPs, standards need to be created for modifying and adapting the EBPs while maintaining their fidelity.