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1. The effectiveness of the inclusion product of piroxicam with beta-cyclodextrin was compared to that of free piroxicam on inflammatory reactions by using three experimental inflammatory models in rats. 2. The inclusion compound showed anti-inflammatory effects similar to those of simple piroxicam on granuloma tissue formation and arthritis induced by complete Freund adjuvant. 3. In carrageenin-induced pleurisy, the piroxicam beta-cyclodextrin reduced leukocyte mobilization more intensely than non-complexed piroxicam. 4. These results suggest that beta-cyclodextrin is a useful tool for improving the efficacy of piroxicam.

In rats of the Holtzman strain, susceptible to the development of adjuvant induced arthritis (AIA), oral administration of BCG significantly inhibited the development of the disease. Oral treatment with purified protein derivative (PPD) had no effect. In the resistant Buffalo rats, however, oral administration of BCG and PPD enhanced the lesions. Since oral administration of antigens has been described to induce suppressor cells, our results suggest that the development of AIA is controlled by suppressor mechanisms, which fail to be activated in the susceptible strain, but are stimulated by the oral administration of BCG.

Injection of complete Freund's adjuvant into one paw of Holtzman rats induced an inflammatory response in the injected site (primary lesion) and from the 10th day on, severe polyarthritis developed (secondary lesions). In this susceptible strain, cyclophosphamide dose dependently reduced the intensity of the primary and secondary lesions. In contrast, in Buffalo rats, which are considered as resistant, cyclophosphamide in the dose of 25 mg/kg significantly potentiated the secondary lesions. Higher doses (200 and 300 mg/kg) also reduced the intensity of the lesions in this strain. Our data suggest that the development of adjuvant induced arthritis is controlled by a cyclophosphamide sensitive suppressor cell population.

The subpopulations of lymphocytes (W3/25+ and OX8+) in the blood, spleen and lymph nodes were analyzed comparatively in rats susceptible (Holtzman) and resistant (Buffalo) to the development of adjuvant induced arthritis (AIA). In naive rats, it was found that the ratio (T helper/T suppressor) was significantly higher in Holtzman compared to Buffalo rats suggesting that the susceptible rats possess less suppressor cells than the resistant. Following induction of AIA (7 and 14 days) the ratio T helper/T suppressor was not significantly different in either strain. When the resistant strain was treated with 25 mg/kg of cyclophosphamide, the T suppressor cells were significantly reduced and this was followed by a strong potentiation of the AIA. Our data suggest that susceptibility to AIA is related to alterations in the T suppressor cell subset.

Using electron microscopy and morphometric methods to assess secretion, we previously found that two times tidal volume ventilation of isolated perfused rat lung stimulates secretion by bronchiolar Clara cells; this effect is not prevented by beta-adrenergic blockade (J. Clin. Invest. 1981. 67: 345-351.). In this study we used the isolated perfused rat lung and the anesthetized mechanically ventilated rat, to further study the mechanism by which large tidal volumes stimulate secretion by Clara cells. With the perfused lung we found (a) alpha-adrenergic inhibition did not block the secretory effect of ventilation at two times normal tidal volume; (b) indomethacin completely blocked the secretory action of two times tidal volume ventilation; (c) medium previously used to perfuse lungs ventilated at two times tidal volume, but not medium previously used to ventilate lungs at normal tidal volume, stimulated secretion by Clara cells when used to perfuse fresh lungs ventilated at tidal volume; (d) addition of prostacyclin to the fresh perfusate increased secretion by Clara cells of lungs ventilated at normal tidal volume. In anesthetized mechanically ventilated rats, sighs stimulated secretion by Clara cells; this increased secretion was inhibited by indomethacin but not by cholinergic blockade (bilateral vagotomy). These studies indicate that increased volume ventilation stimulates secretion by Clara cells in vivo and in vitro; they provide evidence that chemical nonadrenergic, noncholinergic mechanisms are involved in this secretion, and that prostaglandins may be the chemical messenger coupling the mechanico-secretory events.

Leucopenic rats were injected i.v. with either allogeneic or syngeneic lymphocyte suspensions and their capacity to respond to carrageenin tested at various intervals after the injection of the cells. The carrageenin-induced inflammatory response, which is characteristically attenuated in leucopenic animals, was partially but none the less definitely restored when allogeneic cells were transfused 20 min before the irritant, and less so when they were given 1 or 2 h before. Syngeneic cells were effective in restoring this response up to 2 h after injection. Only a small fraction of the exogenous cells, either allogeneic or syngeneic, remained in the blood, and this for short intervals. One hour after administration of cell suspensions blood leucocyte counts again attained previous values. The same rate of disappearance of the cells from blood was observed in splenectomized rats. Removal of the cells from circulation was thought to reflect "homing" into lymphoid tissues and other tissues, but not selectively in the spleen. Lymphocyte constituents, obtained by cell disintegration and injected i.v. into leucopenic rats, did not cause any change in blood leucocyte counts and yet restored the previously inhibited inflammatory response to carrageenin, as much as the viable cells. It is suggested that inflammation-producing materials, either deposited in tissues or formed or transformed at a site of injury, might gain access to the lymphatics during the early stages of a non-immune, inflammatory response, and "stimulate" lymphoid cells in adjacent lymphoid tissues either to release pro-inflammatory factors or to migrate to the site of injury, where they would exert pro-inflammatory activities. Apparently, only a small number of these cells in involved in the response.