IL-35, an anti-inflammatory cytokine which expands CD4+CD25+ Treg Cells.

Interleukin 12 (IL 12) p35/p40 is a heterodimeric cytokine which plays a critical role in inflammation, immunity and tissue proliferation, and also plays a relevant function in T helper (Th) cell polarization and Th1 T-cell differentiation. IL-12 family members, IL-12p70, IL-23, IL-27 and IL-35, play an important role in influencing helper T-cell differentiation. EBV-induced gene 3 can be associated with the p35 subunit of IL-12 to form the EBI3/p35 heterodimer, also called IL-35. It has been shown that IL-35 has biological activity and able to expand CD4+CD25+ Treg cells, suppress the proliferation of CD4+CD25- effector cells and inhibit Th17 cell polarization. IL-35 has been shown to be constitutively expressed by regulatory T (Treg) cells CD4(+)CD25(+)Foxp3(+) and suggested to contribute to their suppressive activity. IL-35 is a crucial mediator which provokes CD4+CD25+ T cell proliferation and IL-10 generation, another well-known anti-inflammatory cytokine, along with TGFbeta cytokine. These studies suggest that IL-35, together with other successfully discovered cytokine inhibitors, represents a new potential therapeutic cytokine for chronic inflammation, autoimmunity and other immunological disorders.

Impact of RANTES, MCP-1 and IL-8 in mast cells.

Chemokines are cytokines with chemotactic properties on inflammatory cells and other cell types. RANTES, MCP-1 and related molecules, constitute the C-C class of chemokine supergene family and a group of cytokines produced by hematopoietic cells, while IL-8 constitute the C-X-C class. The roles of most of these chemokines are not well known, although members of the chemokine family are inflammatory agents. The C-C chemokine plays a role in regulating Th-cell cytokine production and leukocyte trafficking. In this study we clearly show that RANTES and MCP-1 are mediators of acute inflammatory responses. Our report describes additional biological activities for RANTES, MCP-1, and IL-8, suggesting that these chemokines play a fundamental role in histamine and serotonin generation and cell function in mast cells.

Blood to interstitial fluid volume ratio in chronic hypokalaemic states.

The distribution of extracellular fluid over the intra- and extravascular spaces was determined in hypokalaemic and normokalaemic patients. In six patients with Bartter's syndrome, four with pseudo-Bartter's syndrome, and twenty with essential hypertension (EH) chronically treated with chlorthalidone, serum potassium (serum K+) and extracellular fluid volume (ECFV) were decreased, while plasma volume (PV) and blood volume (BV) were normal (see Table 1 for means, standard deviations, and levels of significance). Consequently, the ratio of BV to interstitial fluid volume (IFV) was increased. In ten patients with EH on long-term combined enalapril chlorthalidone therapy, eight EH patients on long-term spironolactone treatment, and twenty-three EH patients treated by short-term sodium restriction, PV, BV, and ECFV were decreased, but serum K+ and BV/IFV were normal. In six patients with primary hyperaldosteronism (PHA) serum K+ was decreased, while PV, BV, and BV/IFV were elevated. Significant negative correlations between sK and BV/IFV were found in the Bartter patients (r = -0.88) and the pooled data of all patients (r = -0.50). These findings suggest an association between chronic hypokalaemia and a fluid shift from the extra- into the intravascular space. The hypothesis that this phenomenon is due to a decreased venous resistance as a consequence of chronic hypokalaemia is discussed.