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Core pentapeptides and an octapeptide (Peptide T) computer deduced from amino acid sequences from vasoactive intestinal peptide (VIP) and the 120 gp external envelope of the HIV (AIDS) virus and synthesized have been reported to have important in vitro and in vivo activity including inhibition of HIV binding to CD4 surface antigens of brain cells and lymphocytes and limitation of HIV infectivity. Two of these core pentapeptides, peptide TTNYT (Peptide T [4-8]) and peptide TDNYT (VIP [7-11]), are reported here, on acute infusion into cannulated afferent popliteal lymphatics of sheep, to produce prompt and marked depressions in the output of both small recirculating and blast lymphocytes into popliteal lymph node efferent lymph. As with a prior VIP infusion study, there appeared to be a selective effect on T4 (CD4) lymphocytes, with a marked predominance of T4 (CD4) lymphocytes in the lymphocyte depleted efferent lymph.

Induced systemic arterial hypotension by intravenous nitroprusside administration and by acute arterial occlusion in sheep have been found to reduce lymphocyte traffic as mirrored in the output of lymphocytes into the efferent lymph of peripheral lymph nodes. In the present series of experiments in sheep with chronically cannulated efferent lymphatics of peripheral lymph nodes, induced and monitored systemic arterial hypertension with intravenous pump infusions of phenylephrine or dopamine both produced sharp increases in the output of lymphocytes into efferent lymph in all of 27 studies. The increases in lymphocyte output with dopamine were more sustained and less associated with evidence of lymphoid tissue damage than with phenylephrine. Phenylephrine infusions were attended by a high incidence of gross bleeding into the efferent lymph, of increased coagulability of efferent lymph in the absence of gross bleeding and of prolonged depression of lymphocyte outputs after the cessation of intravenous infusion.

Vasoactive intestinal peptide (VIP) is a 28 amino acid-residue neurovascular and gut peptide with a number of important biological activities. Recent in vitro studies suggest an immunomodulatory (depressant) role for VIP. In the present in vivo studies, employing the Hall and Morris sheep lymphocyte traffic model, acute infusions of VIP into cannulated afferent lymphatics of popliteal lymph nodes produced prompt and marked depressions in the output of both small recirculating and blast lymphocytes into popliteal efferent lymph, with a selective effect on T4 (CD4) lymphocytes. It has been suggested that the HIV (AIDS) virus may employ VIP or VIP-like receptors on brain cells and lymphocytes for intracellular access.

General anaesthesia of sheep with ketamine and xylazine has been found to produce a profound and prolonged depression in lymphocyte traffic through primary peripheral lymph nodes, as mirrored in the output of lymphocytes into efferent lymph. In this study, the depression has been found to be associated with a marked and sustained elevation in prostaglandin E2 (PGE2) levels in efferent lymph. The degree and duration of lymphocyte output depression was found to be modulated (diminished), both in degree and duration, by study-node drainage-area stimulation from prior surgery, inflammation or bacterial immunization. Even when the anaesthesia-associated lymphocyte-output depression was modulated by drainage-area inflammation, the period of lymphocyte-output depression was correlated still with elevated levels of PGE2 in efferent lymph. When drainage-area stimulation was produced by bacterial immunization (killed Salmonella muenchen), the anaesthesia-associated depression in lymphocyte output into efferent lymph (small as well as blast) was accompanied by a depression in antibody output into efferent lymph.

Substance P, an 11 amino acid residue vasoactive neurotransmitter peptide, has been found on acute infusion (50 micrograms) into cannulated afferent lymphatics of popliteal lymph nodes of sheep to produce marked elevations in both efferent lymph flow and in the outputs of both blast and small recirculating lymphocytes into popliteal node efferent lymph (chronically cannulated). These elevations were characterized by a delay in the onset of major elevations, a marked prolongation of the elevations and a substantially greater stimulative effect on the output of blast lymphocytes. It is suggested that the number and types of substance P receptors on lymphocytes and in sheep peripheral lymph nodes may be responsible for these observations. Infusion of substance P, known for involvement in pain impulse transmission, was able to briefly overcome anaesthesia-induced depression in lymphocyte traffic. The substance P-induced alterations in lymph flow and lymphocyte traffic in vivo were demonstrated to be due to local rather than systemic effects of substance P.