concanavalin-a and glycylglutamine

The objectives of this study were to determine the effects of dietary glycyl-glutamine (Gly-Gln) on postweaning growth, small intestinal morphology, and immune response of stressed or nonstressed piglets. Pigs (n = 144; initially 4.49 kg and 14 d of age) were randomly allocated to 24 pens (6 pigs/pen) in an environmentally controlled nursery and assigned to Escherichia coli lipopolysaccharide (LPS) challenge (PBS vs. LPS) and Gly-Gln supplementation (0 vs. 0.15%) in a 2 x 2 factorial arrangement of treatments with 6 pens/treatment. The LPS was the stress-inducing agent, and it was injected on d 7 and 14 of the 21-d experiment. Inflammatory challenge with LPS reduced ADG (P < 0.05) and tended to reduce ADFI (P = 0.06) of piglets from d 7 to 21 of the experiment. Supplementation of Gly-Gln increased ADG and G:F from d 0 to 21 (P < 0.05). On d 21 (1 wk after the second LPS injection), there was an LPS challenge x diet Gly-Gln interaction for ADFI (P < 0.05), but it was difficult to ascertain whether Gly-Gln increased ADFI. A trend for an LPS challenge x diet Gly-Gln interaction was observed for ADG (P = 0.07). There were no differences in lymphocyte proliferation among treatments. The LPS challenge increased crypt depth (CD) of the duodenum and decreased the ratio of villus height (VH) to CD of the ileum (P < 0.05) on d 14 (1 wk after the first LPS injection), whereas dietary supplementation of Gly-Gln increased VH of the ileum and VH:CD of the duodenum (P < 0.05). The concentration of peripheral blood IL-1beta was increased by injection of LPS (P < 0.05) and was decreased by dietary Gly-Gln supplementation during the experimental period (P < 0.05); however, there was no interaction of LPS challenge x Gly-Gln addition for IL-1beta concentration. Concentrations of peripheral blood IL-2 tended to increase at d 14 (P = 0.09) and soluble IL-2 receptor tended to decrease at d 7 (P = 0.06) in piglets supplemented with Gly-Gln; therefore, the peripheral blood IL-2/soluble IL-2 receptor system tended to favor the secretion of IL-2 during the first 2 wk of the experiment. In conclusion, considerable suppression of growth and immune function occurred in early weaning piglets challenged with LPS, and such depression could be alleviated by dietary Gly-Gln supplementation independent of the LPS challenge.

Topics: Animals; Concanavalin A; Cytokines; Diet; Dietary Supplements; Dipeptides; Escherichia coli; Immunity; Immunity, Cellular; Intestine, Small; Lipopolysaccharides; Lymphocyte Activation; Swine

Human MPF (Lys-Lys-Gly-Glu) stimulates the proliferative response of human lymphocytes to the T-cell mitogen concanavalin A by 121-751% in the concentration range 10(-11)-10(-4) M; the peak effect is at 10(-8) M, lower or higher concentrations eliciting reduced responses, i.e. the dose-response curve is bell-shaped. Species specificity is high. Human MPF similarly stimulates rat lymphocytes, but the peak effect is seen at a 100-fold higher dose (10(-6) M). Rat MPF (Lys-Lys-Gly-Gln) has a peak effect at 10(-6) M with human lymphocytes, but the peak effect with rat lymphocytes is at a 1000-fold lower dose (10(-9) M). Truncated forms of the MPFs (Gly-Glu, Gly-Gln, Gly, Glu, Gln) and opioid peptides (beta-endorphin, [Leu] and [Met]enkephalin) show insignificant or only weak stimulatory or inhibitory effects. These results suggest that MPF acts via specific non-opioid receptors located on lymphocytes and that endogenously released MPF may have an important role in the functioning of the immune system.

Topics: Animals; beta-Endorphin; Cell Division; Concanavalin A; Dipeptides; Dose-Response Relationship, Immunologic; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Glutamic Acid; Glycine; Humans; Lymphocyte Activation; Mitogens; Oligopeptides; Peptide Fragments; Rats; Species Specificity; T-Lymphocytes

Glycyl-L-glutamine (GLG), the carboxy terminal dipeptide of B-endorphin, inhibits brainstem neuronal activity. It also occurs along with B-endorphin in pituitary secretory vesicles suggesting a neurosecretory role for this dipeptide. We have evaluated potential immunoregulatory actions of this compound using the Phytohemaglutinin (PHA) blastogenesis and the concanavalin A (ConA) suppressor cell induction assays. GLG in low doses (10(-12) M) enhanced the response of human lymphocytes to PHA induced blastogenesis, however; with higher doses of the dipeptide (10(-7) M) immunosuppression was consistently observed. In the suppressor cell induction assay, when GLG was used together with ConA, we observed a dose-dependent inhibition of suppressor activity. These results clearly indicate that GLG produces a dose dependent bidirectional modulation of at least two indicies of immune function, and confirm the presence of a second pituitary peptide with the potential for potent immunomodulatory action.

Topics: beta-Endorphin; Concanavalin A; Dipeptides; Dose-Response Relationship, Drug; Endorphins; Humans; Immunity; Lymphocyte Activation; Male; Phytohemagglutinins; T-Lymphocytes, Regulatory

beta-endorphin (10(-7) M) induced suppressor cell activity in human peripheral blood lymphocyte cultures comparable to that of concanavalin A (Con A) (60 micrograms/ml). beta-endorphin and Con A, when used together during the induction portion of the suppressor assays, displayed synergistic activity. In contrast, glycyl-L-glutamine, the carboxy terminal dipeptide of beta-endorphin, inhibited development of Con A induced suppressor activity. It appears that the previously reported suppressive effects of beta-endorphin on immune function may be achieved by activation of specific suppressor T cell populations.

Topics: beta-Endorphin; Concanavalin A; Dipeptides; DNA Replication; Endorphins; Humans; Kinetics; Lymphocyte Activation; Male; T-Lymphocytes, Regulatory