Publications

Though lectin mitogen stimulation of T-cell proliferation is an interleukin 1- (IL 1), interleukin 2- (IL 2) dependent process, the calcium ionophore A23187 may be able to initiate T-lymphocyte proliferation by an additional pathway. That the action of A23187 is IL 1 independent was demonstrated by its ability to stimulate monocyte-depleted cells without the addition of exogenous IL 1. The IL 2 independence of A23187 was indicated by (i) the inability of exogenous IL 2 to augment A23187-induced proliferation and (ii) the inability of the monoclonal antibody anti-Tac (with specificity for the human IL 2 receptor) to inhibit proliferation mediated by A23187. By contrast, in cultures stimulated with the lectin mitogen phytohemagglutinin, additional IL 2 considerably increased proliferation, whereas anti-Tac routinely caused 60-90% inhibition. Although the ionophore caused some IL 2 production and resulted in IL 2 receptor expression, quantitative studies showed that our results could not be explained by excessive amounts of endogenous IL 2 interfering with the blocking action of the antibody. Therefore, these data suggest that the action of A23187 as a human lymphocyte mitogen may be the result of at least two pathways--one dependent on the interleukin-cell interactions and the other independent of these mediators.

We studied the relationship between cough and bronchoconstriction caused by inhaled distilled water aerosol in 8 subjects with asthma by measuring specific airways resistance (SRaw) and recording cough while subjects breathed serially increasing volumes of distilled water or normal saline aerosol produced by an ultrasonic nebulizer. We performed the distilled water dose-response curves after no treatment and after treatment with cromolyn aerosol, lidocaine aerosol, or atropine aerosol in doses of 0.2 mg and 2.0 mg on separate days. Without prior treatment, distilled water aerosol caused cough in 7 of 8 subjects and a marked increase in SRaw in every subject, whereas saline aerosol did not cause cough or a greater than 50% increase in SRaw in any subject. The 2 doses of atropine caused an equivalent reduction in baseline SRaw, but 2.0 mg caused greater inhibition of water-induced bronchoconstriction than did 0.2 mg. Neither dose of atropine inhibited cough. These data suggest that water-induced bronchoconstriction involves cholinergic nerves and that water-induced cough is not dependent on bronchoconstriction. Lidocaine inhibited cough but not bronchoconstriction, whereas cromolyn inhibited bronchoconstriction but not cough, suggesting that cromolyn does not inhibit bronchoconstriction by a generalized inhibition of airway afferent nerves.

A 25-year-old man developed severe shortness of breath, constricting chest pressure, chest pain, cough and myalgia following acute exposure to a waterproofing aerosol that contained trichloroethane. He became febrile and developed a small area of atetectasis with significant hypoxemia. Recovery was complete within 36 hours. This experience suggests that casual use of a trichloroethane aerosol with a surface active agent can cause acute pulmonary toxicity. The mechanism of this injury is unknown.