Objectives-A generalised transient improvement may follow intra-articular administration of glucocorticoids to patients with inflammatory arthropathy. This may represent a systemic anti-inflammatory eVect of glucocorticoid released from the joint, mediated through processes such as altered leucocyte traYcking or suppressed release of pro-inflammatory cytokines. Patients, who had received intraarticular injections of glucocorticoids were therefore studied for evidence of these two systemic eVects. Methods-Patients with rheumatoid arthritis were studied. Peripheral blood leucocyte counts, tumour necrosis factor (TNF ) release by peripheral blood monocytes, blood cortisol concentrations, and blood methylprednisolone concentration were measured for 96 hours after intraarticular injection of methylprednisolone acetate. Results-Measurable concentrations of methylprednisolone were present in blood for up to 96 hours after injection. Significant suppression of the hypothalamic-pituitary-adrenal axis persisted throughout this time. Altered monocyte and lymphocyte traYcking, as evidenced by peripheral blood monocytopenia and lymphopenia, was apparent by four hours after injection and resolved in concordance with the elimination of methylprednisolone. Granulocytosis was observed at 24 and 48 hours. Release of TNF by endotoxin stimulated peripheral blood monocytes was suppressed at four hours and thereafter. Suppression was maximal at eight hours and was largely reversed by the glucocorticoid antagonist, mifepristone. Conclusions-After intra-articular injection of methylprednisolone, blood concentrations of glucocorticoid are suYcient to suppress monocyte TNF release for at least four days and to transiently alter leucocyte traYcking. These eVects help to explain the transient systemic response to intra-articular glucocorticoids. Suppression of TNF is principally a direct glucocorticoid eVect, rather than a consequence of other methylprednisolone induced changes to blood composition.

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Age-related loss of muscle mass and strength is widely attributed to limitation in the capacity of muscle resident satellite cells to perform their myogenic function. This idea contains two notions that have not been comprehensively evaluated by experiment. First, it entails the idea that we damage and lose substantial amounts of muscle in the course of our normal daily activities. Second, it suggests that mechanisms of muscle repair are in some way exhausted, thus limiting muscle regeneration. A third option is that the aged environment becomes inimical to the conduct of muscle regeneration. In the present study we used our established model of human muscle xenografting to test whether muscle samples taken from cadavers, of a range of ages, maintained their myogenic potential after being transplanted into immunodeficient mice. We find no measurable difference in regeneration across the range of ages investigated up to 78 years of age. Moreover, we report that satellite cells maintained their myogenic capacity even when muscles were grafted 11 days postmortem in our model. We conclude that the loss of muscle mass with increasing age is not attributable to any intrinsic loss of myogenicity and is most likely a reflection of progressive and detrimental changes in the muscle micro-environment such as to disfavor the myogenic function of these cells.