Induction of an acute erosive monarticular arthritis in mice by interleukin-1 and methylated bovine serum albumin.

We examined the effect of interleukin-1 (IL-1) administration on a mild and transient inflammatory response in the knees of mice injected intraarticularly with methylated bovine serum albumin (mBSA). Injection of mBSA on day 0 into nonsensitized mice caused a weak inflammatory response confined to the infrapatellar fat pads and involved infiltration by mononuclear cells, neutrophils, and eosinophils. The response developed between days 4 and 7 and resolved by day 28. No erosion of cartilage or subchondral bone was seen. In contrast, mBSA-treated mice injected with recombinant human IL-1 beta subcutaneously in the ipsilateral footpad on days 0-3 developed a severe monarticular arthritis in the antigen-injected knee. Pannus developed, extending over the articular surfaces, and extensive erosion of cartilage and subchondral bone occurred. Multinucleated giant cells, together with fibrin-like material, were observed at sites of active bone erosion and debris, and large numbers of neutrophils were seen in the joint space. These pathologic features represent a new arthritis model in which IL-1 profoundly augments a weak inflammatory response and induces acute erosive joint destruction, supporting the hypothesis that IL-1 is an important cytokine in the pathogenesis of arthritis.

Hypertension as related to renal function in diabetes mellitus.

The relationships between blood pressure and renal function were investigated in 78 hypertensive patients with diabetes mellitus type I or II. Renal function was assessed by determining the glomerular filtration rate and the para-aminohippurate clearance in 32 and serum creatinine in 46 subjects. In the latter, the reciprocal serum creatinine, corrected for age and changing creatinine/insulin clearance ratio, was used as an estimate of glomerular filtration rate. In the 54 patients with serial determinations, the duration of follow-up averaged 10.5 years. In older patients with type II diabetes without clinical proteinuria, hypertension developed either before or after the onset of diabetes. When it appeared, renal function was only slightly reduced. During follow-up, the decline in reciprocal serum creatinine averaged 2.7% per year, a figure very similar to that found in nondiabetic patients with benign essential hypertension. It did not correlate with the blood pressure. In patients with a proteinuria greater than 2.5 g per day and histologic and/or clinical evidence of diabetic glomerulosclerosis, the severity of hypertension correlated inversely with the level of renal function. The rate of decline in function averaged 11% per year but varied widely. It was not significantly related to the blood pressure. These data suggest that different types of hypertension (essential, diabetic, and nephrogenic) may be associated with diabetes mellitus. The rate of decline in renal function is closely related to the presence or absence of clinical proteinuria but not to the level of blood pressure.

Rate of functional deterioration in polycystic kidney disease.

Renal function was evaluated in 44 patients with adult polycystic renal disease at different stages of the affection. In 38 patients single or serial determinations of the glomerular filtration rate and the effective renal plasma flow were performed. In 21 of these patients and in an additional group of six subjects, serial determinations of serum creatinine were obtained. The data show that renal function does not decrease at a constant rate between birth and endstage renal failure. It remains well preserved for many years but decreases rapidly at a later stage. The relationship between indices of renal function (glomerular filtration rate, PAH-clearance and/or reciprocal serum creatinine) and the age of the patients might be described adequately by assuming that the impairment in renal function is proportional to the growth of the cysts and that the radius of the cysts increase at a slow but constant rate. Possible contributory factors are secondary infection and hypertension.