investigation objective: To investigate the pathogenesis of lung injury in Pneumocystis carinii pneumonia and nonspecific interstitial pneumonitis (NIP).

investigation objective: To investigate the pathogenesis of lung injury in Pneumocystis carinii pneumonia and nonspecific interstitial pneumonitis (NIP), universal pulmonary complications of human immunodeficiency virus (HIV) infection. The efficacy of corticosteroid therapy in P carinii pneumonia and the observation that bronchoalveolar lavage (BAL) neutrophilia predicts a poor prognosis support the premise that the lung injury of P carinii pneumonia is suitable to the host's inflammatory answer to the infection.

Design: In vitro measurements forward previously collected BAL fluid samples.

Setting: The Clinical Center of the National Institutes of Health, a research hospital and tertiary care referral center

Patients: Five normal offers 5 asymptomatic HIV-positive patients, 10 HIV-positive patients with NIP (5 asymptomatic and 5 with respiratory symptoms), and 19 HIV-positive patients with P carinii pneumonia.

Measurements and results: BAL leukotriene [Bsub4] ([LTBsub4]) interleukin 8 (IL-8), and phospholipase [A.sub.2] ([PLA.sub.2]) were measured. IL-8 and [PLA.sub.2] were elevated in patients with P carinii pneumonia, and IL-8 correlated with BAL fluid absolute neutrophil compute [LTB.sub.4], IL-8, and [PLA.sub.2] of the same heights were elevated in patients with NIP; [LTBsub4] and [PLA.sub.2] of the same heights correlated with absolute neutrophil calculate and IL-8 correlated with alveolar-arterial oxygen constraining force difference. IL-8 was elevated in the asymptomatic HIV-positive patients, and there was a direction toward elevation of [PLA.sub.2] in this group

Conclusion: IL-8 appears to play a part in the pathogenesis of lung injury in P carinii pneumonia and may be the principal neutrophil chemotaxin in this disease; [PLA.sub.2] may also be involved in the pathogenesis of P carinii pneumonia. the two [LTB.sub.4] and IL-8 may be involved in the recruitment of neutrophils and following lung injury of NIP. These data allude to that there are varying mechanisms on which inflammatory cells are recruited to the lung in different HIV-related lung diseases.

Pulmonary complications of human immunodeficiency virus (HIV) infection are habitual causes of morbidity and mortality among patients with AIDS. Pneumocystis carinii pneumonia has been the chiefly common index diagnosis of AIDS and is among the most numerous frequent causes of death.[1,2] Nonspecific interstitial pneumonitis (NIP), characterized by way of diffuse alveolar damage and macrophage or lymphocytic infiltration, or one as well as the other is a common cause of pulmonary disease in HIV-infected patients. NIP is identified in up to 32 percent of all episodes of HIV-related pneumonitis, moreover rarely causes respiratory failure.[3,4] The etiology of NIP is not known.

not long ago anecdotal evidence and uncontrolled trials of corticosteroid therapy for P carinii pneumonia have given way to a growing consensus, based forward several well-designed studies, that corticosteroids are beneficial as adjunctive therapy in patients with stern P carinii pneumonia.[5-8] The efficacy of corticosteroid therapy in P carinii pneumonia, the observation that bronchoalveolar lavage (BAL) neutrophilia predicts a poor prognosis and is a marker for more methodical disease,[9-14] and mounting laboratory evidence[15-19] support the premise that the lung injury of P carinii pneumonia is befitting to an inflammatory response elicited in the legion by the organism and is done by both cellular and humoral mechanisms.

The demonstration of phospholipase activity in bronchoalveolar secretions of experimental animals with P carinii pneumonia, whether derived from entertainer or organism, suggests several possible mechanisms of cellular injury.[20] Phospholipase [A.sub.2] ([PLA.sub.2]) hydrolyze membrane phospholipids, producing membrane-damaging lysophospholipids and clear fatty acids,[21] and has been implicated in the pathogenesis of adult respiratory distress syndrome[2223] [PLA.sub.2] action also liberates arachidonate, which is metabolized to strong proinflammatory substances, the eicosanoids. Among the eicosanoids, leukotriene [Bsub4] ([LTBsub4]) is a efficient neutrophil chemotaxin in vivo and in vitro,[24-27] and may play a part in the lung injury of adult respiratory distress syndrome[28] bacterial pneumonia,[29] and asbestosis.[30] Interleukin-8 (IL-8), a cytokine produc principally by dint of mononuclear phagocytes but also on alveolar epithelial cells,[31] is another powerful neutrophil chemotaxin and activator.[32] Interleukin-8 has been implicated in the pathogenesis of adult respiratory distress syndrome and idiopathic pulmonary fibrosis,[33,34] and may be the major neutrophil chemotactic factor in the lung[31]

We have measured [LTBsub4] IL-8, and [PLA.sub.2] activity in BAL fluid from HIV-infected patients with P carinii pneumonia and NIP as well as from asymptomatic HIV-positive patients and normal proffers and correlated these markets of acute inflammation with clinical and laboratory evidence of the severity of respiratory disease. These observations should help to define the character of these inflammatory mediators in the pathogenesis of HIV-related lung disease.

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