Experimental models of hypersensitivity pneumonitis.

Experimental models of hypersensitivity pneumonitis are important tools for the study of the pathogenesis of this disease. In this paper we review the characteristics of the main animal models developed until now. The HP models in rats seem to be particularly appropriate for studying pigeon fancier's disease and the HP induced by chemicals, as well as for studying mediators of acute lesions induced by immunocomplexes. However, the HP models developed in rats are of less value in the evaluation of other aspects of the pathogenesis of this clinical entity in humans. The murine models of HP offer several advantages: the ease and simplicity of intranasal administration, the ability to produce acute and subacute pulmonary lesions similar to those found in humans, the possibility of reproducing lesions similar to those of nonaffected exposed subjects and the possibility of pharmacologically modulating the process. Their disadvantages lie in the different pulmonary lymphocyte response and the difficulty in reproducing a model of chronic fibrosis. The HP models in rabbits are extraordinarily useful for evaluating the immunological mechanisms through which subjects repeatedly exposed to the antigen do not develop clinical manifestations. However, the rabbit has several immunological differences when compared to humans, and the effect of some immunomodulators in this animal is different. The models of HP in guinea-pigs have as advantages the ease in handling the animals, the possibility of pharmacological manipulation, and the ability to induce an acute phase that is very similar to that observed in humans. The drawback, however, is the low lymphocyte response and the striking eosinophilic reaction that contrast with the bronchoalveolar data found in HP in humans. In conclusion, there is no ideal model to reproduce all the findings observed in humans, suggesting that the experimental animal and the method of developing HP should be selected on the basis of concrete research aims.     

Union after multiple anterior cervical fusion: 21 cases followed for 1-6 years

With a mean follow-up of 3 (1-6) years, we report on 21 patients who underwent multiple level cervical fusion, using autologous iliac crest grafts. Dis-cectomies were performed in 14 patients and cor-pectomies in another 7. Instrumentation was used in all patients with colectomies and in 2 patients who underwent 2-level and 3-level discectomies. Non-union occurred in 1 patient at 1 level. Graft displacement requiring reoperation was observed in 2 patients with massive corpectomies, in 1 of them as a consequence of trauma. In both patients complete bony fusion was obtained after reoperation and no other complications were observed. We conclude that the success rate with multiple-level fusion is comparable to that of single-level fusion when adequate fixation is achieved.     

Experimental pulmonary fibrosis induced by paraquat plus oxygen in rats: a morphologic and biochemical sequential study

Changes in lung structure and collagen metabolism were studied at 1, 2, 3, 4, 6, and 8 weeks in a model of pulmonary fibrosis induced in rats with paraquat plus hyperoxia. Morphologic examination of the lungs revealed that the earliest lesions consisted of severe and irreversible endothelial and alveolar epithelial cell damage. Afterward, an inflammatory process took place, initially dominated by polymorphonuclear leukocytes and then by mononuclear cells, but with the constant presence of granulocytes. From the fourth week on there were fibroblast proliferation and a moderate increase of mast cells. In the early stages alveolitis was focal, but from the second week the lungs were diffusely affected with severe distortion of the architecture. Collagen content was moderately increased in the first 2 weeks and then showed a progressive increment until the end of the experiment. Collagen synthesis was significantly elevated from the fourth week, coinciding with interstitial fibroblast proliferation, although there were some animals that showed increased collagen production from the first week. Collagenolytic activity occurred in 3 stages: at 2 weeks there was increased collagen degradation, at 3, 4, and 6 weeks the values showed a trimodal behavior, and at 8 weeks almost all experimental rats presented an important decrease of collagenolysis. Thus, the development of lung fibrosis was associated first with increased rates of collagen synthesis and later with a decrease of collagen degradation.     

Suppressor T-cell population induced by Junin virus in adult mice.

Intracerebral (i.c.) Junin virus (JV) infection of adult BALB/c mice is characterized by the absence of morbidity and a low mortality (barely 8-10%). In contrast, the suckling mouse model exhibits almost 100% mortality following central nervous system (CNS) alterations consistent with a delayed-type hypersensitivity (DTH)-like immune response. Besides, JV infection of adult (resistant) mice leads to immunosuppression of DTH to unrelated antigens. Here we present evidence demonstrating that such suppression is mediated by JV-induced cells present in spleen from 24 hr to 24 days post-infection, bearing the Thy-1+, Ly-1+2- phenotype and reactive to an unrelated antigen such as sheep red blood cells (SRBC). No evidence of suppressor factors was found. A relatively low number of total splenic cells (5 x 10(6) cells/mouse) was enough to transfer suppression. Therefore, this cell population may be involved in adult mouse survival to JV infection.     

Correlation between cyclophosphamide-induced viral susceptibility and depletion of Junin virus-induced suppressor populations.

In contrast to lymphocytic choriomeningitis virus, another arenavirus, Junin virus (JV), the etiologic agent of Argentine hemorrhagic fever, when inoculated into suckling mice, induces lethal meningoencephalitis characterized by a delayed-type hypersensitivity (DTH)-like immune response. However, the adult BALB/c mouse is resistant to infection and no DTH reaction can be seen. This different viral sensitivity may be related to the development of an antigen non-specific DTH-suppressor cell pathway at work in the adult mouse. When the resistant mice are treated with cyclophosphamide (Cy) (50 mg/kg each dose) given at days -1,+1,+4 (zero: infection day), animals become susceptible and develop DTH reaction in brain that leads to death. We analyze the influence of the timing of Cy administration on the suppressor system developing after infection. It was found that Cy depletes the previously described JV-induced suppressor populations (Tsv) but a new suppressor cell (Tsv*) is disclosed bearing the Thy 1+ Ly1+2- phenotype which is unable to depress DTH in Cy-treated animals. With only two doses of Cy corresponding to days -1 and +1, the target of Tsv* cells is depleted but the third dose is still required to achieve full depletion of Tsv cells which are able to employ the Cy-resistant antigen-specific suppressor cells as targets. Since the Cy treatment is able to deplete the Tsv population together with the target of Tsv* cells, animals became unable to regulate lethal DTH reaction. Thus, a cellular explanation for an empirically established Cy schedule able to abrogate the adult mouse resistance to JV is proposed.     

Quantification of bacteria in the small intestine of malnourished children with chickenpox

The purpose of the present study was to determine whether a high number of bacteria could be demonstrated in the upper small bowel during the chickenpox infection. Intestinal juice was drawn in nine malnourished children, during and two weeks after the acute period of the disease. The results of the study fail to demonstrate quantitative differences in the bacterial flora of the small bowel in both periods. Besides that, the bacterial overgrowth previously reported in malnutrition, is confirmed.