Immunomodulatory potential of thymulin-Zn(2+) in the alveolar epithelium: amelioration of endotoxin-induced cytokine release and partial amplification of a cytoprotective IL-10-sensitive pathway.

The immunomodulatory potential of thymulin in the perinatal epithelium is not well characterized. In an in vitro model of fetal alveolar type II epithelial cells, we investigated the exhibition of an anti-inflammatory activity of this peptide hormone. Thymulin selectively ameliorated, in a dose-dependent manner, the endotoxin-induced release of IL-1 beta (IC(50) = 657 ng. ml(-1)), but showed no inhibitory effect on IL-6 and TNF-alpha. Zinc, an anti-inflammatory antioxidant, which is required for the biological activity of thymulin, reduced the secretion of IL-1 beta (IC(50) = 62 microM), TNF-alpha (IC(50) = 1000 microM), and, to a lesser extent, IL-6. This cation (100 microM) amplified the effect of thymulin on IL-1 beta and TNF-alpha (IC(50) < 0.1 ng. ml(-1)), but not on IL-6. Analysis of whether thymulin is up-regulating a counterpart anti-inflammatory signaling loop revealed the involvement of an IL-10-sensitive pathway. These results indicate that thymulin acts as a novel dual immunoregulator by enhancing an anti-inflammatory cytoprotective response and depressing an inflammatory signal, an effect synergistically amplified, in part, by cationic zinc.

Humoral and cell-mediated immunopotentiation in vaccinated chicken layers by thymic hormones and zinc.

The humoral and cell-mediated immunities to a trivalent killed vaccine, administered subcutaneously to white leghorn-chicken layers at 29 and 31 weeks of age, and containing antigens of infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), and Newcastle disease virus (NDV), were quantitated in five vaccinated and one unvaccinated-control group. Four out of the five vaccinated groups were immunopotentiated by various combinations of zinc and thymic hormones administered intraperitoneally in a volume of 0.1 ml per bird at an interval of three days for a period of three weeks, starting at 29 weeks of age. At each time interval, each bird of the first group received thymulin (10 ng) and ZnCl2 (1 microM), while each bird of the second group received thymopoietin (25 ng) and ZnCl2 (1 microM); in the third group, each bird received thymulin (10 ng), thymopoietin (25 ng), and ZnCl2 (1 microM), while each bird of the fourth group received only ZnCl2 (1 microM). Birds of the fifth group were only vaccinated and the control birds in the sixth group were left without vaccination or other immunopotentiation. Among all combinations, the thymulin-ZnCl2 resulted in birds with the highest humoral immunopotentiation to IBV, IBDV, and NDV antigens with respective percent increase in the mean titer at 33 weeks of age, compared with initial titer at 29 weeks of age, equivalent to 199%, 671.7%, and 86.4%. The highest cell-mediated delayed hypersensitivity reaction, measured at 48 h following an intradermal administration of the trivalent vaccine in the wattles at 33 weeks of age, was obtained in chickens immunopotentiated by the thymulin-thymopoietin-ZnCl2 combination.

Calcium homeostasis during therapeutic plasma exchange.

Because the removal of substantial quantities of plasma calcium during plasma exchange is rarely attended by clinically significant hypocalcemia, we evaluated calcium homeostasis during this procedure. Twenty-one procedures were performed on 10 patients with various neurological disorders. The reduction by plasma exchange in the serum concentrations of total calcium, ionized calcium, magnesium, and phosphate was significantly less than predicted (p less than 0.001) based on plasma volume of the patient and size of the exchange. However, N-terminal parathomone (PTH) levels increased to 242 +/- 120 percent midway into the procedure and were 207 +/- 84 percent after plasma exchange; urinary cyclic adenosine monophosphate (cAMP) levels rose by 165 +/- 35 percent. These data demonstrate a rapid compensatory response in N-terminal PTH and urinary cAMP to the reduction by plasma exchange of serum concentrations of total calcium, ionized calcium, and phosphate. The routine administration of supplemental calcium during plasma exchange may therefore be unnecessary in patients with normal parathyroid function.