Influence of a Co-stimulation of human leucocytes with an Escherichia coilpreparation and fixed immunoglobulins on cytokine release in the presence of hydro cortisone

Pharmaceuticals of biological origin consisting of bacterial culture suspen sions (BCS) as active ingredients have long been used for the treatment of hemorrhoidal diseases and chronic anal pruritogenic eczemas. However, some of these pharmaceuticals often contain glucocorticoids such as hydrocortiso ne as an anti-inflammatory supplement. Therefore, the question arises wheth er the claimed Immunostimulatory capacity of the bacterial culture suspensi on might be altered by the steroid. Up to now numerous reports support the evidence that the stimulation of the different Fc-receptor subtypes on leuc ocytes result in profound immunoregulatory activities influencing phagocyto sis and antigen processing, antibody-dependent cytotoxicity or secretory fu nctions thereby enhancing the overall activities of the immune system towar ds foreign antigens/pathogens. With these findings in mind it was investiga ted whether the immunomodulatory capacity(s) of the BCS in the presence of hydrocortisone will be modified by solid-phase bound Immunoglobulins (Igs). For this purpose freshly prepared human peripheral blood leucocytes (PBLs) were incubated with different concentrations of the BCS (0.1, 1, 10 mug/ml ), either with or without fixed human immunoglobulins in the presence of in creasing concentrations of hydrocortisone. As a parameter of PBL activation the secretion of different cytokines was measured, e.g. tumor necrosis fac tor alpha (TNF-alpha), interleukin-10 (IL-10) and granulocyte-macrophage co lony stimulating factor (GM-CSF). Cytokines were determined with specific s andwich ELISAs. With this modified cell culture system it was demonstrated that the immunosuppressive activities, normally caused by hydrocortisone, w ere partially antagonized by the combination of BCS plus fixed Igs. TNF-alp ha and GM-CSF were significantly more produced, even in the presence of hyd rocortisone, whereas the synthesis of IL-10 was diminished by fixed Igs. Ho wever, this effect could he reversed with increasing concentrations of hydr ocortisone. These results raise the possibility that in the natural environ ment, e.g the rectal mucosa, antigens derived from the BCS are bound by spe cific Igs, thereby modifying secretory and effector functions of locally pr esent leucocytes in another way as free antigens. The biological relevance of these in vitro data with respect to the therapeutic benefit of the BCS p reparations with hydrocortisone will be discussed considering recent findin gs in the literature.