Intravenous immunoglobulin (IVIG) attenuates antibody binding in acute haemorrhagic immunopneumonitis in a rat model of complement-dependent lung injury

Administration of rabbit anti-rat lung serum (PNTS) to rats produces a fulm inant haemorrhagic pneumonitis sensitive to the availability of complement. The present experiments were undertaken to assess whether a high dose of I VIG can affect the development of this kind of cytotoxic reaction. The expe rimental design included groups of Wistar rats pretreated intravenously wit h physiologic saline, IVIG or a preparation of human F(ab')(2) fragments. O ne hour later the animals were challenged with either saline or PNTS. At 30 min after challenge, blood was collected and the lungs were removed. Pulmo nary damage was evaluated by light microscopy; C3 deposits and the binding of immunoglobulins to the alveolar septa were assayed by immunofluorescence . The serum complement activity of the classical and alternative pathways w as estimated by a kinetic technique. Pretreatment with IVIG decreased bindi ng of rabbit anti-lung antibodies to alveolar septa and prevented the depos ition of C3. These results indicate that pretreatment with IVIG inhibits th e binding of the pathogenic antibody to lung tissue. Human IgG binding was not detected in any animal. The protection against lung injury afforded by pretreatment with IVIG, in contrast to the pneumotoxic effect of PNTS obser ved in control animals, was evident despite the administration of F(ab')(2) to the rats. Since pretreatment with F(ab')(2) failed to prevent the acute lung lesion, our results indicate that the attenuation afforded by IVIG in this model of complement-dependent tissue injury seems to be related to th e integrity of the IgG molecule.