Library

Notes: The recent findings that bicycle exercise training may reduce the number of swollen joints in patients with rheumatoid arthritis (RA) stimulated us to examine the possibility that this was mediated through exercise-induced immunomodulation. The effect of a single bout of physical exercise on blood mononuclear subsets, proliferative responses and natural killer (NK) cell activity was determined. Six patients with moderately active RA for 20 years exercised for 27 min on a bicycle, the work intensity being estimated at 68% of max V̇O2max. Blood samples were collected before and during the last minutes of exercise, as well as 2 h afterwards. During bicycle exercise the proportion of T cells (DC3+ cells) declined, mainly because of a fall in T helper cells (DC4+ cells). The proportion of NK cells (CD16+ cells) increased during work, but reverted afterwards. The monocytes (CD14+ cells) did not change; B cells (CD20+ cells) declined slightly during exercise and reverted later. No change in PHA-, PPD- and Unstimulated BMNC proliferation occurred during exercise. Two hours after exercise, PPD- and IL-2-induced proliferation increased significantly, except for the PHA-stimulated response. The NK cell activity increased only significantly during exercise when the cells were preincubated with indomethacin, and returned to normal 2 h afterwards. This shows that brief, moderate exercise by patients with RA alters the composition of blood mononuclear cell subsets and cell functions. The clinical significance of this immunomodulation remains to be elucidated.

Notes: Cellular immunity was measured under resting conditions in 29 highly trained male racing cyclists during a period of low training intensity (winter), and in 15 untrained people. Fifteen of the cyclists were reexamined during a period of high training intensity (summer) together with 10 of the untrained people. Data on lymphocyte subpopulations, natural killer cell activity and lymphocyte proliferative responses were obtained. Changes in any of these immune parameters from low to high training seasons did not differ significantly between the trained and untrained people. The natural killer cell activity was significantly higher in the cyclists, both during the period of low training intensity (39.2±11.6%vs 30.9±6.4%) and during the period of high training intensity (55.2±18.4% vs 33.6±20.3%). Leucocyte, lymphocyte and neutrophil concentrations did not differ between the two groups. The blood mononuclear cell (BMNC) subsets, including CD3+, CD4+, CD8+ and CD16+ cells, and the BMNC proliferative responses following stimulation with either interleukin 2, purified derivative of tuberculin or phytohaemagghitinin did not differ significantly between the groups.

Notes: The immunomodulatory drug isoprinosine has been found to delay the occurrence of opportunistic infections in HIV-infected individuals. To elucidate the mechanism of action, eight HIV-positive, healthy patients were treated with isoprinosine, 3 g/day for 28 days; six patients received no treatment but were examined in parallel, and two patients were withdrawn. All patients had blood collected just before the start as well as on days 14 and 28 of isoprinosine treatment.Isoprinosine significantly enhanced the lymphoproliferative response after stimulation with phytohaemagglutinin (PHA) and purified derivative of tuberculin (PPD), while isoprinosine had no effect on the following immune parameters: the expression of surface markers on blood mononuclear cells including CD2, CD3, CD4, CD8, CD14, CD19, CD20, CD25, leu-8, and HLA-DR. Furthermore isoprinosine did not influence the ability of interleukin 2 (IL-2) to stimulate the proliferation of lymphocytes or the natural killer (NK) cell activity either unstimulated or stimulated in vitro with alpha interferon (IFN-α), IL-2. or indomethacin. Neither did isoprinosine affect the in vitro production of (IL-1) α or β, IL-2, IL-6. or tumour necrosis factor (TNF).

Notes: The present study was designed to examine the effect of physical exercise on human natural killer (NK) cells. Six healthy volunteers underwent two different acute physical exercise tests with an interval of at least 1 week: (1) 60min bicycle exercise at 80% of maximal oxygen uptake (VO2max) and (2) 60 min back-muscle training at up to 29% of VO2max; blood samples were collected before and during the last few minutes of exercise, as well as 2 h and 24 h afterwards. The NK cell activity (lysis/fixed number of mononuclear cells) increased during bicycle exercise, dropped to a minimum 2 h later and returned to pre-exercise levels within 24 h. Back-muscle exercise did not significantly influence NK cell activity. Plasma levels of adrenaline, noradrenaline, and cortisol were elevated during bicycling, but not during back-muscle exercise, indicating that exercise intensity is a determinant of NK cell activity. During bicycle exercise the NK cell subset (CD 16+ cells) of mononuclear cells increased significantly. Furthermore an improved interleukin 2 (IL-2) boosting of the NK cell activity was found during work as compared to IFN-α and indomethacin-enhanced NK cell activity. These results indicate that NK cells with a high IL-2 response capacity are recruited to the peripheral blood during exercise. The decreased NK cell activity demonstrated 2 h after work was probably not due to fluctuations in size of the NK cell pool, since the proportion of CD16+ cells was normal. The finding that indomethacin fully restored the suppressed NK cell activity in vitro and the demonstration of a twofold increase in monocyte (CD20+ cells) proportions 2 h after work, strongly indicate that prostaglandins released by monocytes during the heavy physical exercise are responsible for the down-regulation of the NK cells.

Notes: The present study was designed to examine the effect of physical exercise on subsets and proliferative responses of blood mononuclear cells. Sixteen young, healthy volunteers underwent 60min of bicycle exercise at 75% of maximal oxygen uptake (VO2max). After an interval of at least 1 week, six of the subjects underwent a 60-min back muscle training period at up to 30% of VO2max. Blood samples were collected before and during the last minutes of exercise, as well as 2 and 24 h later. Blood mononuclear cell (BMNC) subpopulations were determined and the proliferate responses after incubation with phytohaemagglutinin (PHA) or purified derivative of tuberculin (PPD), were quantified by [3H]thymidine incorporation. During bicycle exercise the relative blood concentration of T cells (CD3+ cells) declined, mainly due to a fall in T helper cells (CD4+ cells). The natural killer (NK) cell subset (CD16+ cells) increased during work, but reverted after; the monocytes (CD14+ cells) increased 2 h after work, whereas the B-cell subset (CD20+ cells) did not change. BMNC subsets were not significantly changed by back muscle exercise. The PHA-induced proliferative response decreased during bicycle exercise, whereas the PPD-induced response did not change. No significant changes occurred during back muscle exercise. Investigation of subgroups after incubation with [3H]thymidine showed that the proliferative response per CD4+ cell did not change in relation to exercise, but the contribution of the CD4+ subgroup to proliferation declined during bicycle exercise due to the decreased proportion of CD4+ cells. The suppression of the PHA response during bicycle exercise can be explained in part by a relative fall in CD4+ cells. The pool sizes of BMNC subfraction may be elicited by increased catecholamine and cortisol levels.

Notes: Interleukin 1 (IL-1) is involved in the early activation of T lymphocytes. The CD4 antigen, described as a phenotypic marker of helper T cells, is also important in early T-cell activation by its ability to hind to MHC class II molecules on antigen-presenting cells, and to transmit positive (and negative) signals to the cells. We observed that purified human monocyte IL-1 as well as recombinant IL-1α and IL-1β selectively decreased the binding of monoclonal antibodies to CD4 on the surface of otherwise unstimulated blood T cells, in contrast to prestimulated and continuously grown CD4+ cells. Under optimal growth conditions, the initial reduction in antibody binding to CD4 was followed by an apparent re-expression of the CD4 antigen even in the presence of high concentrations of IL-1. This re-expression did not occur if the cells were cultured at 4°C, or after treatment with actinomycin D or cytochalasin B, indicating that protein synthesis and intact microfilament function were essential for re-expression of CD4 binding. The mechanism by which CD4 molecules are physically and/or functionally modulated by IL-1 is unclear.

Notes: Recent investigations have demonstrated that the primary mixed lymphocyte reaction (MLR) is dependent on certain accessory molecules, e.g. CD4 and LFA-1. We have compared the requirements of the primary MLR and the responses of alloreactive, primed lymphocytes (PL) by inhibition studies using monoclonal antibodies (MoAb) directed against (i) adhesion molecules belonging to the CD11 cluster of leucocyte antigens (CD11a, LFA-1; CD11b, MAC1=CR3; and CD11c, p 150.95); (ii) various T cell-related antigens(CD2, CD4, CD5 and CD8); and (iii) recombinant IL-1β. The CD5-, CD11a- and CD11c-reactive MoAb significantly inhibited the primary MLR (inhibition = 25%, P〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:03009475:SJI405:les" location="les.gif"/〉0.01; 48%, P〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:03009475:SJI405:les" location="les.gif"/〉0.01, and 13%, P〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:03009475:SJI405:les" location="les.gif"/〉0.05, respectively) but these MoAb did not inhibit the primed lymphocyte reaction (PLR). The CD11b-reactive MoAb had no significant influence on either of the responses. CD2- and CD4-reactivc MoAb significantly inhibited both primary MLR (〉80%, P〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:03009475:SJI405:les" location="les.gif"/〉0.01) and to a lesser extent the PLR (40–65%, P〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:03009475:SJI405:les" location="les.gif"/〉0.01). A MoAb reactive with IL-1β inhibited the primary MLR (38%, P〈0.01) and the purified protein derivative (PPD) induced lymphocyte transformation response (42%, P〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:03009475:SJI405:les" location="les.gif"/〉0.01) of peripheral blood mononuclear cells (PBMC), whereas primed allogeneic responses to PBMC and Epstein-Barr virus (EBV) cell lines were unaffected by this MoAb. In addition, preliminary data indicated that PL seemed neither to bind exogenous IL-1 (as opposed to CD4+ PBMC) nor to possess membrane-bound IL-1. The differences between ‘virgin’ and primed, allogeneic T-cell responses indicate that profound changes in the functional capability of the responding T-cell population take place during the bulk expansion. The results indicate that during repeated priming with alloantigen and bulk expansion, the proliferative response of T lymphocytes becomes independent of (i) the interaction with the CD11 adhesion molecule(s). (ii) the CD5 molecule, and (iii) the cytokine IL-1β.