Both tumor necrosis factor a (TNF-a) and transforming growth factor 13 (TGF-1) are found in synovial fluid from arthritic joints of humans and of rodents with experimental arthritis. The role of endogenously produced TGF-fi and TNF in the pathogenesis of collagen type U-induced arthritis (CIA) in DBA/1 mice was examined by determining the effect of neutralizing monoclonal antibodies to these factors on the course of the disease. Endogenously produced as well as systemically administered TGF-P1 and TNF-a had opposite effects, since TGF-(31 and anti-TNF protected against CIA, whereas anti-TGF-fi and TNF-a increased CIA incidence and/or severity. Intraperitoneally Injected TGF-13 at a dose of 2 pg per day for 14 days signficantly ameliorated arthritis, even when started at the time of arthritis development, although it did not reverse established disease. The resistance to CIA induction caused by a prior intravenous injection of collagen type H was not significantly influenced by the simultaneous injection of TGF-,13, TNF-a, or interleukin la. It is concluded that the endogenous production of TNF and TGF-1 is important in determining the course of CIA.

Interleukin 1 (IL-1) and tumor necrosis factor a are thought to contribute to the inflammatory response associated with autojinmune diseases. Transforming growth factor ( (TGF-i) counteracts many effects of these cytokines and has various immunosuppressive properties. In the present study, it is shown that microgram amounts of TGF-(31, injected daily for 1-2 weeks, protect against collagen-induced arthritis (CIA) and relapsing experimental allergic encephalomyelitis (REAE), the animal models for rheumatoid arthritis and multiple sclerosis, respectively. When administered during induction of the disease, TGF-g31 prevents CIA but only delays the onset of REAE by 2-3 days. However, when administered during a remission, TGF-fl1 prevents the occurrence of relapses in REAE. The results suggest that TGF-,B1 has powerful anti-inflammatory effects, mimicking in some respects the beneficial effects of immunosuppressive drugs in these experimental models ofautoimmune disease, but without discernable adverse effects.

Defining tumor cell immune evasion Mouse models used to study cancer often lack a full immune system, allowing implantation of human tumors into the mice. By contrast, naturally evolving tumors must contend with a fully functional immune system and its destruction of some of the cells (see the Perspective by Ho and Wood). Two groups now report studies on mouse models with a fully intact immune system. Martin et al . started with preexisting murine tumor cell lines and examined their continued evolution in vivo, whereas Del Poggetto et al . examined the development of new pancreatic tumors in the context of inflammation, as is often seen in human patients. In each study, the authors found that the immune system exerted a selective pressure on cells that would give rise to tumors, promoting the survival of those that had lost expression of tumor suppressor genes or activated a specific oncogene. The findings suggest a major role for the immune system in driving tumor evolution across multiple types of cancer. —YN