• Toxocara canis: Het effect van behandeling met anti-interleukine-5 en anti-interleukine-4 op immunologische en ontstekingsparameters in de longen

      Buijs J; Pitstra B; Rouws C; Rees E van; Savelkoul HFJ; LPM; VUA/celbiologie en immunologie; EUR/MF (1995-01-31)
      Toxocara canis-infected BALB/c mice were treated with rat hybridoma cells producing either anti-interleukin-5 (anti-IL-5) or anti-IL-4 to inhibit increases in eosinophils and immunoglobulin E respectively. The aim of the investigation was to study the effect of this inhibition on the course of pulmonary inflammation caused by T.canis migrating larvae. Anti-IL-5 producing cells administered i.p. (1 x 1000000) two days before and 5 days after infection inhibited completely the eosinophil increases in blood and bronchoalveolar lavage fluid (BALF). The albumin concentration in the BALF of infected mice increased significantly. Treatment with anti-IL-5 or with isotype control did not affect this increase, showing that eosinophils apparently played a minor role in the observed change in microvascular permeability. Lung tissue sections stained to demonstrate IL-5 and IFN-gamma positive cells showed their absence in non-infected mice and in infected mice treated with anti-IL-5. In the lungs of isotype and saline-treated infected controls IL-5 positive cells were present although their number was low. Remarkable was that anti-IL-5 treatment, and to a less extent isotype treatment, of infected mice caused a huge increase in IFN-gamma positive cells. These results suggested that administration of rat proteins to T.canis-infected animals promoted the increase of IFN-gamma positive cells and apparently stimulated T helper 1 cells. Anti-IL-4 treatment seemed unsuccessful. Administration of 1,5 x 1000000 cells at day 0 and 1 x 1000000 at day 7 p.i. did not have any effect on the cell populations in the BALF. Anti-IL-4 inhibited the IgE increase in infected mice with about 70% in both, serum and BALF at 14 days p.i. but no inhibition was observed at 28 days p.i.. Isotype treatment even stimulated IgE production in infected mice. The persisting presence of larvae and thus of antigen caused a continuous stimulation of the immune response with emphasis on the T helper 2 cells. Prolonged stimulation seemed to induce a type of B-epsilon cells producing IgE independent of IL-4. Inhibition of specific cytokines using non-self proteins, in this case rat proteins, may cause unexpected, and unwished, side effects.