Malnutrition and experimental lung allergy.

BACKGROUND: Although it is commonly accepted that the immune response is affected by malnutrition there are very few data about its effect in allergic diseases. OBJECTIVE: The aim of the present study was to investigate the effect of malnutrition in allergic lung inflammation. METHODS: An anaphylactic reaction was induced in rat lungs and the increased vascular permeability was measured in the trachea, internal and external bronchi and parenchyma by the Evans blue extravasation method. These studies were conducted in two dietary groups: one fed a normoproteic diet (18%) and the other a hypoproteic diet (4.5%). When the animals were 60 days old the group fed the hypoproteic diet presented a reduction of 77.86% in bodyweight, 63.3% in food intake and 36% in plasma protein concentration characterizing a severe protein-calorie malnutrition. RESULTS: The anaphylactic reaction in the lungs induced a significant increase in vascular permeability in the trachea and bronchi of both dietary groups. However, the intensity of this effect was significantly lower in the malnourished group. Analysis of immunoglobulin isotypes in the serum by ELISA showed that whereas IgG1 and IgG2a levels were similar in both groups, the levels of IgE were significantly lower in the malnourished animals. Moreover, the levels of antigen-specific IgG1, IgG2a and IgE were all significantly inhibited by the protein-calorie malnutrition. When antibodies were passively transfered to the malnourished rats, they developed a reaction as intense as the normoproteic group. CONCLUSION: These results suggest that the capacity to release inflammatory mediators and the vascular response to these mediators is not affected by this type of malnutrition and, therefore, the diminished response of the airways reported here is probably due to the lower levels of anaphylactic antibodies produced by the malnourished rats.

In vivo interleukin-4 regulation of antibody responses in euthymic and athymic mice to a T-independent antigen (hydroxyethyl starch).

The aim of this work was to analyze the implication of IL-4 in the antibody response induced in vivo after immunization with a class II T-cell-independent (TI) antigen. IL-4 suppression, through administration of a rat monoclonal antibody antimurine IL-4 (11B11), in euthymic BALB/c mice during the course of immunization with the DNP-coupled hydroxyethyl starch (TI antigen), inhibited the production of anti-DNP IgG1 antibodies, potentiated the synthesis of IgG2a and had no effect on the other isotypes (IgM, IgG2b and IgG3). After IL-4 treatment of athymic BALB/c mice in the same conditions, although the IgG2a production was not increased, the IgG1 synthesis was significantly decreased, as was observed in euthymic mice. These results demonstrate that cytokine IL-4 plays an active role in vivo in the regulation of antibody response after immunization by a T-cell-independent antigen, in normal as well as in nude mice. The origin of IL-4 in these animals and especially in those athymic mice remains to be determined.

The perinatal presence of antigen (p-azophenylarsonate) or anti-mu antibodies lead to the loss of the recurrent idiotype (CRIA) in A/J mice.

The immune response of A/J mice against p-azophenylarsonate (Ars)-keyhole limpet hemocyanin (KLH) is characterized by the dominance, late in primary and during the secondary, of a recurrent idiotype called CRIA, encoded by a canonical combination of Ig gene segments. In this study, A/J mice were given Ars coupled to deaggregated human gamma globulins (dHGG) within 24 h after delivery. The offsprings from these mice were then exposed as adults to Ars-KLH. These animals developed an unusual immune response. The level of anti-Ars antibodies was nearly normal but a dramatic shift in repertoire was observed: the cross-reactive idiotype which is the hallmark of the anti-Ars response in A/J mice was completely absent. The idiotype could be recovered by injection of anti-idiotypic antibodies alone, with no need of lipopolysaccharide coupling. Therefore the presence of antigen at birth can lead to a strong perturbation of idiotype selection. Similar results were obtained with neonatal treatment using anti-IgM antibodies. After recovery of suppression, A/J mice can mount an anti-arsonate response of normal level but devoid of the dominant idiotype.

In vivo study of mIgM and mIgD cross-linking on murine B cells.

In this study, we have analysed in mice the effects on the immune response of in vivo treatment with different rat monoclonal antibodies (MoAb) against IgM and IgD. Although the effects of IgD cross-linking have been studied already, no attempt has been made to characterize the effects of in vivo IgM crosslinking, probably because of the higher IgM serum levels compared to IgD. We have used a panel of nine monoclonal rat anti-mouse IgM and three anti-IgD antibodies and we have characterized their isotypes, avidities, immunoglobulin (Ig) cross-linking and internalization abilities. Our results show that injection of mice with some rat MoAb against IgM led to an important decrease of IgM serum level and internalization of membrane IgM (mIgM) on almost all B cells. Similarly, treatment with a high-avidity anti-IgD antibody induced disapperance of mIgD on B cells. Treatment with rat MoAb against IgM or IgD led to a synthesis of specific antibodies and there was a direct relationship between the Ig internalization abilities of rat MoAb and the induction of specific antibody production. Finally, treatment with a high-avidity rat MoAb against IgD induced a polyclonal IgE and IgG1 secretion. The significance of these results on mIg receptor functions is discussed.