International Journal of Immunopathology and Pharmacology

The role of the platelet activating factor in human B lymphocyte responses to Interleukin-2 was examined and compared with that of Interleukin-4 by assessing the ability of this molecule to modulate proliferation and differentiation. Highly purified B lymphocytes were prestimulated for 48 h with Staphylococcus aureus Cowan Strain I and then were cultured with Interleukin-2 alone or in combination with either Interleukin-4 or the platelet activating factor and the proliferation (after 3 days) and the immunoglobulins (IgG and IgM) production (after 7 days) were evaluated. When SAC-activated B lymphocytes were preincubated overnight with PAF (0.0001 to 1 μM) or with IL-4 (1 to 100 U/ml) both the IL-2-induced proliferation and immunoglobulins secretion were inhibited. This inhibition was not a reflection of a decreased expression of the IL-2 receptor (CD25) because this expression was not modified on SAC-activated B lymphocytes after preincubation with either PAF or IL-4. Moreover, this suppression effect was not the result of a delayed response to IL-2.

The PAF-induced suppression was overcome in the presence of PAF antagonists (BN 52021 and BN 50730) but was not modified in the presence of a neutralizing anti-IL-4 antiserum. On the other hand, the IL-4 mediated suppression was totally reversed in the presence of the neutralizing anti-serum and only marginally reversed in the presence of the PAF antagonists. These results indicate that both PAF and IL-4 may exert a number of immunoregulatory actions on human B lymphocyte proliferation and differentiation. They interfere with the stimulation of activated B lymphocytes by IL-2 and could play an important immunoregulatory role in the determination of isotypic regulation in the specific humoral responses.

The number of airway epithelial cells (AEC) in bronchus lumen after various types of anaphylactic shock of similar intensity was determined in guinea pigs. Aerosol-induced anaphylactic shocks were studied after four types of active sensitization: sensitization by IM injection of 30 mg/kg ovalbumin mixed with Freund's complete adjuvant; sensitization by IM injection of 30 mg/kg ovalbumin; sensitization by IP injection of 1 μg ovalbumin and 50 mg A1 (OH)₃ by animal; sensitization by 2 exposures to 1%-ovalbumin aerosol at a 7-day interval. One, 3,6,24 and 48 h after the anaphylactic reaction the number of AEC in bronchoalveolar lavage fluid (BALF) was counted in comparison to guinea pigs sensitized but exposed to 0.9% NaCl aerosol. The number of AEC was significantly increased only 24–48 h after the shock in animals sensitized with ovalbumin in Freund's complete adjuvant. In animals passively sensitized by antiserum obtained with sensitization by ovalbumin in Freund's complete adjuvant and challenged by IV or aerosol administration of antigen, non rise in the number of AEC was obtained 24–48 h after the shock. The higher amount of AEC 24–48 h after the anaphylactic reaction in animals actively sensitized by ovalbumin in Freund's complete adjuvant could be related to the higher increase in the number of neutrophils and of mononuclears obtained in the BALF at these times in comparison to other types of active sensitization. The rise in the number of AEC only after the active reaction seems to show the part played by T-lymphocytes in the induction of this effect. The increase in the number of eosinophils in BALF and the appearance of the hyperreactivity cannot be related to the rise in the AEC in bronchus lumen.

The syngeneic anti-anti-idiotypic antibodies (Ab3) IgG, -IgM, and -IgA induced by polyclonal mouse anti-idiotypic antibodies (Ab2) against the rabbit F(ab) T. spiralis-Ab1, was studied. IL-6 level and cytotoxic activity (TNFα and LT) in the serum of mice infected with L1-T. spiralis or immunized with T. spiralis-Ab2 antibodies were also determined. The Ab1 antibody response was found to reflect the life cycle of the parasite. High IgA-, IgM-, and IgG-Ab1 levels, as well as corresponding levels of cytotoxic activity (62.3, 88.8 and 107.8 5/ml) and IL-6 (216, 447 and 789 U/ml) on days 10, 20 and 28 after the infection, respectivelly, were detected. The Ab3 antibody response against the polyclonal T. spiralis-Ab2, followed the classical pattern of antibody level after initial infection with an immunogen. IgM was first detected 10 days p.i., while IgA and IgG were detected 20 days p.i. Cytotoxic activity of 93.2, 245.9, and 326.7 U/ml, and IL-6 levels of 237, 304, and 487 U/ml, were detected on 10, 20, and 28 days p.i., respectivelly. Although Ab3 bound to T. spiralis-Ab2 antibodies or to L1-T-spiralis antigen and cytotoxic activity in mice immunized with T. spiralis-Ab2 antibodies was increased, there was no protection against the parasitic infection.

The production of the cytokines IFN-gamma, IL-2, IL-1-alpha and TNF-alpha was investigated in the supernatants of mitogen-stimulated whole blood cell cultures from 52 oral contraceptive users, 33 pregnant women and 75 female controls. Cells from women taking oral contraceptives produced significantly less IFN-gamma (p≤0.05) and TNF-alpha (p≤0.05) compared to the controls. In the cultures of the pregnant women significantly lower levels of IFN-gamma (p≤0.01), IL-2 (p ≤0.001) and TNF-alpha (p≤0.01) were found than in those of the controls. Total and differential leukocyte counts were almost identical in all three groups of women. It is suggested, that lymphocyte and monocyte function as measured by cytokine production is altered in women taking oral contraceptives and in pregnant women.

The effects of vinpocetine (VP), a proposed modulator of production of arachidonic acid metabolites, on disease development and immune functions in rats with adjuvant-induced arthritis (AA) were investigated. Daily i.p. administration of VP (25 mg/kg/for 14 days) to rats with adjuvant-induced arthritis significantly reduced both edema and bone erosion in the hindpaws. After the administration of vinpocetine a decrease of serum hyaluronic acid levels, active lymphocyte number and increase of serum albumin levels were found. Decrease in urine biopterin levels were normalised after treatment with VP.

In conclusion, vinpocetine was shown to have antiinflammatory and antiarthritic effects in rats.

In a previous work we reported that treatment with indomethacin, aspirin and piroxicam in inbred BALB/c mice bearing a transplantable fibrosarcoma induced by methylcholanthrene produced tumor regressions in 45, 32 and 30 per cent of the animals, respectively. In the remaining mice, in which there was no tumor regression, tumor volumes varied (small 0.05<0,5 cm³ medium 0,5<1,35 cm³ and large > 1,35 cm³).

In this histological study we observed that the antitumoral effect of these nonsteroidal antiinflammatory drugs occurred together with a remarkable tumor encapsulation and a decrease in the physical characteristics of malignancy of the tumor cells. The tumor-associated macrophages, which can be detected only by the iron-dextran phagocytosis but not by that of colloidal carbon or trypan blue, were found in the peritumoral area in all cases under study. Their numbers and/or phagocytic capacity were slightly increased in both regressing and small tumors with respect to large, medium and control tumors. These findings suggest that the action of these prostaglandin synthesis inhibiting drugs would permit tumor encapsulation by an improvement in the macrophage-fibroblast relationship together with a decrease in the malignancy of the tumor cells.