In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT02054481 ).

The peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors belonging to the nuclear receptor superfamily. Until recently, the genes regulated by PPARs were those believed to be predominantly associated with lipid metabolism. Recently, an immunomodulatory role for PPARγ has been described in cells critical to the innate immune system, the monocyte/macrophage. In addition, evidence for an antiinflammatory role of the PPARγ ligand, 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) has been found. In the present studies, we demonstrate, for the first time, that murine helper T cell clones and freshly isolated splenocytes express PPARγ 1. The PPARγ expressed is of functional significance in that two ligands for PPARγ, 15d-PGJ2 and a thiazolidinedione, ciglitazone, mediate significant inhibition of proliferative responses of both the T cell clones and the freshly isolated splenocytes. This inhibition is mediated directly at the level of the T cell and not at the level of the macrophage/APC. Finally, we demonstrate that the two ligands for PPARγ mediate inhibition of IL-2 secretion by the T cell clones while not inhibiting IL-2-induced proliferation of such clones. The demonstration of the expression and function of PPARγ in T cells reveals a new level of immunoregulatory control for PPARs and significantly increases the role and importance of PPARγ in immunoregulation.

Boehringer Ingelheim.

SummaryUncertainty regarding pathogenic mechanisms has been a major impediment to effective prevention and treatment for human neurologic diseases such as multiple sclerosis, tropical spastic paraparesis, and AIDS demyelinating disease. Here, we implicate lymphotoxin (LT) (tumor necrosis factor (3 [TNF-0]) and TNF-ci in experimental allergic encephalomyelitis (EAE), a murine model of an autoimmune demyelinating disease. In this communication, we report that treatment of recipient mice with an antibody that neutralizes IT and TNF-a prevents transfer of clone-mediated EAE . LNC-8, a myelin basic protein-specific T cell line, produces high levels of IT and TNF-ot after activation by concanavalin A, antibody to the CD-3e component of the T cell receptor, or myelin basic protein presented in the context of syngeneic spleen cells . LNC-8 cells transfer clinical signs of EAE. When LNC-8 recipient mice were also treated with TN3 .19 .12, a monoclonal antibody that neutralizes IT and TNF-ci, the severity of the transferred EAE was reduced, while control antibodies did not alter the disease . The effect of anti-LT/TNF-cx treatment was long lived and has been sustained for 5 mo. These findings suggest that IT and TNF-ci and the T cells that produce them play an important role in EAE.

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