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Interleukin 10 (IL-10) is a cytokine with both antiinflammatory and immunosuppressive properties. In the present study, we have examined the effects of recombinant human IL-10 (rHuIL-10) on the development of acute graft-vs.-host disease (GVHD) in unirradiated (C57B1/6JxA/J) F1 recipients of parental A/J lymphocytes. rHuIL-10 (2.5 to 100 micrograms/mouse administered subcutaneously) caused a significant reduction in splenomegaly in GVH mice. GVH splenocytes exhibited an augmented capacity to produce IFN-gamma when stimulated in culture with Con A or LPS. The IFN gamma produced in response to LPS stimulation was found to be derived from CD4+ and CD8+ T cells with little or no contribution from the NK1.1+ subpopulation of the GVH spleen. Treatment with IL-10 in vivo was found to diminish the capacity of splenocytes to produce IFN gamma when stimulated with LPS but not with Con A. IL-10 did not protect GVH mice from a lethal dose of LPS but caused a marked reduction in the serum TNF alpha response triggered by the LPS challenge. We conclude that IL-10 may be useful in controlling those clinical manifestations of acute GVHD that arise as a result of the activities of proinflammatory cytokines such as IFN gamma and TNF alpha.

Rats with either posterior parietal (PPC) or dorsal hippocampal (HIP) lesions were tested for open-field activity, acquisition of a multiple T water maze habit, and presence of a 'cognitive map' of the water maze arena. The performances of control and PPC-lesioned rats were similar on all behavioral measures. However, the HIP-damaged rats demonstrated higher levels of general activity, severe deficits in both working and reference memory in the multiple T water maze task, and failed to develop a cognitive map of the water maze arena.

We studied the dose-response effects of the F(ab')2 fragments of murine monoclonal antibodies to the platelet GPIIb/IIIa receptor (7E3 and 10E5) on in vivo platelet thrombus formation in a well-characterized monkey model in which the carotid artery is stenosed and thrombus formation is provoked and augmented by intimal damage and the infusion of subaggregating doses of epinephrine. Both antibodies abolished thrombus formation with a mean dose of -0.2 mg/kg. Ex vivo platelet aggregation was not always abolished at doses that abolished thrombus formation; similarly, bleeding times were only moderately prolonged (9.1 +/- 1.4 minutes) at these doses. Increasing the dose above that required to abolish thrombus formation consistently produced abolition of ex vivo platelet aggregation, marked prolongation of the bleeding time (14.2 +/- 1.5 minutes), and nearly quantitative blockade of GPIIb/IIIa receptors. We conclude that in a significant percentage of animals, the extent of GPIIb/IIIa blockade required to prevent vasoocclusive thrombus formation in this model is less than that required for abolition of platelet aggregation, and that the preservation of only a minority of functional GPIIb/IIIa receptors might be adequate to maintain a nearly normal bleeding time.

Although viruses have recently been implicated in the pathogenesis of Paget's disease and Perthes' disease, little information is available regarding bone and marrow response to the presence of a noncarcinogenic virus. Vaccinia virus was introduced into the medullary cavity of the femoral shaft of 30 New Zealand White rabbits, and an appropriate control inoculation was performed. Virus was recovered from the inoculation site in 50% of the animals at intervals to one month after inoculation. Histologic abnormalities were observed in 69% of the test femora; similar abnormalities were not observed in the control femora. These abnormalities consisted of bone and marrow necrosis, lymphocyte and plasma cell infiltration, and new bone formation. Some of the newly formed bone was also necrotic. The latter observation suggests an alternative mechanism for the death of new bone, which, in Perthes' disease, has customarily been attributed to repeated ischemic insults.