IL-12-dependent vascular cell adhesion molecule-1 expression contributes to airway eosinophilic inflammation in a mouse model of asthma-like reaction.

Bronchial-alveolar eosinophilic inflammation is among the characteristic pathological changes in asthma, which has been shown to be correlated with type 2 cytokine and chemokine production. Exogenous IL-12 has been found to be inhibitory for pulmonary eosinophilia in reported studies. Using a murine asthma-like model induced by OVA, we found in the present study that IL-12 gene knockout (KO) mice showed substantially reduced airway recruitment of eosinophils compared with wild-type control mice following OVA sensitization/challenge, although the levels of circulating eosinophils were comparable in these two groups of mice. Cytokine analysis showed Ag-driven Th1 (IFN-gamma) and Th2 (IL-4, IL-5, IL-10, and IL-13) cytokine production by CD4 T cells from local draining lymph nodes and spleen. Similarly, local eotaxin production was comparable in wild-type and IL-12 KO mice. In contrast, immunohistochemical analysis showed that the expression of VCAM-1 on the lung endothelium of IL-12 KO mice was dramatically less than that in wild-type mice. Furthermore, administration of rIL-12 at the stage of sensitization and challenge with OVA restored airway eosinophilia and VCAM-1 expression in IL-12 KO mice. The results suggest that endogenous IL-12 contributes to the recruitment of eosinophils into airways observed in asthma, possibly via enhancement of the expression of VCAM-1 on local vascular endothelial cells.

Durable remissions following prolonged plasma exchange in thrombotic thrombocytopenic purpura.

We evaluated the efficacy of prolonged plasma exchange (PEX) for attaining durable remissions in thrombotic thrombocytopenic purpura (TTP). A recent review using steroids or PEX in initial management showed an 80% response rate but produced a relapse rate of 67-84%. Records of 50 patients starting PEX treatment for TTP/HUS were reviewed to identify and select those whose course of treatment had ended over 1 year earlier, whether or not the result was satisfactory. Records were evaluated for outcome, especially remission associated with treatment by "prolonged" plasma exchange. "Prolonged" was defined as continuing PEX beyond the stage where a normal platelet count was attained and until evidence of hemolysis was "minimal or at least compensated." If disease activity as judged by the criteria of hemolysis became accelerated or resumed, PEX was increased by volume of FFP (e.g., from 3 to 4 L) or rate (from less than daily to daily). Of 50 consecutive patients treated by PEX for TTP/HUS there were 40 cases after which at least one year had passed since the end of treatment. These 40 patients were evaluated for the results of treatment by PEX. Eight failed to achieve remission, dying in hospital within 1 month of admission. Twenty-eight achieved remission, sustained for 1 year or more in all. These are the reasons for our enthusiasm about this report. Four achieved remission lasting less than 1 year. Splenectomy was performed to obtain a sustained remission in one patient following administration of three 2 mg doses of vincristine and two relapses.(ABSTRACT TRUNCATED AT 250 WORDS)