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Several studies have indicated to us that certain amino acids may exhibit antiinflammatory activity. In the present study we attempted to evaluate the inhibitory effect of various amino acids on gelatin-induced abdominal inflammation in mice using peritoneal fluid cytology as the diagnostic tool. The L-amino acids tested were tryptophan, phenylalanine, alanine, cystine, hydroxyproline, tyrosine, citrulline, leucine, and valine. Hydrocortisone was used as an antiphlogistic steroid control. Tryptophan, phenylalanine, alanine, cystine, hydroxyproline, and tyrosine all significantly decreased the inflammation. Citrulline and valine, however, both exhibited strong antiiflammatory responses. Based on these results, three related dipeptides were also screened: L-valy-L-alanine, L-valyl-L-tryptophan, and L-tyrosl-L-valine. Valyl alanine was found to produce a strong antiinflammatory effect. In a final test, the combination of the steroid, hydrocortisone, and the amino acid, cystine, was screened for a synergistic effect. The combined treatment inhibited the gelatin-induced inflammation more than either the amino acid or the steroid administered alone.

Human retroviruses have recently been linked with T cell lymphoproliferative disorders and with the acquired immune deficiency syndrome. We investigated the mechanisms for acquired pure red cell aplasia and cutaneous anergy in a patient with the chronic T gamma-lymphoproliferative disease (T gamma-LPD) syndrome. Patient marrow erythroid progenitors (BFU-E) were 17 +/- 9% of control and were selectively increased to 88-102% of control after marrow T cell depletion. Patient Leu 2+ suppressor T cells spontaneously produced high titers of human gamma-interferon and resulted in a concentration-dependent selective inhibition (74-91%) of BFU-E when co-cultured with autologous or allogeneic marrow. Conditioned media (CM) derived from patient Leu 2+ T cells similarly inhibited growth of autologous or allogeneic marrow BFU-E. The inhibitory factor derived from patient CM was acid-labile (pH 2) and sensitive to trypsin; prior treatment of patient T cells with anti-HLA-DR monoclonal antibody plus complement abrogated the suppressive effect of T cell-derived CM. Patient peripheral blood mononuclear cells (PBMC) were unable to support growth of cultured interleukin 2 (IL 2)-dependent T cells, but responded to exogenous IL 2 in vitro with a 16-21-fold augmentation, relative to control, in mitogen-induced proliferation. Antibodies to HTLV-I core proteins p19 and p24 but not to HTLV-III proteins were detected in patient serum by Western blotting; patient cultured PBMC stained (7-11%) with antibodies to p19 and p24. Patient cultured PBMC demonstrated integrated HTLV-I genomic sequences by the Southern technique and expressed both specific HTLV-I genomic sequences by RNA dot blot plus reverse transcriptase activity. Utilizing a cloned DNA probe for the beta chain of the T cell receptor gene, patient PMBC demonstrated gene rearrangements providing presumptive evidence for clonality. The presence in serum of HTLV-I p19 and p24 antibodies, the expression of p19 and p24 core antigens on patient mononuclear cells, the evidence of HTLV-I proviral integration sequences and the expression of HTLV-I genomic sequences in patient cells, indicates infection with HTLV-I and raises the possibility of an etiologic link between human retrovirus infection and some instances of large granular lymphocytic leukemia (T gamma-LPD).