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S Stepkowski

Publications and source records attributed to S Stepkowski.

At least 19 recordsLinked to original sources
PubMed1991

The immunosuppressive antagonism of low doses of FK506 and cyclosporine.

Clinical immunosuppression with potentially toxic agents may be optimized by combining drugs that act synergistically at low doses. The studies presented herein attempted to apply this strategy to the macrolide FK506 and the endecapeptide cyclosporine, which similarly inhibit T cell responses but display distinctive arrays of toxic side effects. The interaction between these agents was subjected to rigorous pharmacologic analysis using the median effect and combination index equations to determine synergistic, antagonistic, or additive drug interactions. FK506 and CsA showed pharmacologic antagonism in inhibiting in vitro proliferation upon phytohemagglutinin, anti-CD3 antibody, and mixed lymphocyte reaction (MLR) stimulation, and interleukin 2 generation by activated normal human peripheral blood lymphocytes. The antagonistic relationship was confirmed in vivo using low doses of FK506 in combination with CsA to treat Wistar-Furth recipients of heterotopic Buffalo rat cardiac allografts, a major plus minor histocompatibility barrier. This antagonistic relation suggests that FK506/CsA combination therapy does not permit dose reduction of the individual drugs to mitigate toxic complications.

Animals↗
PubMed1989

The synergistic effect of total-lymphoid irradiation with extracted donor alloantigen in inducing transplantation unresponsiveness.

The synergistic effect of total lymphoid irradiation with KCl-extracted donor type antigen (H-Ag) was examined in the rat cardiac graft model. TLI therapy alone of 10, 16, and 20 Gy achieved by a 2 Gy daily treatment of WFu recipients produced modest prolongation of BUF heart survival to median survival times (MST) of 11, 26, and 30 days, respectively, in comparison with normal control (MST = 6). The TLI immunosuppressive effect was significantly potentiated with donor H-Ag when combined with 16 (greater than 100 days) but not with 10 or 20 Gy TLI therapy. This effect was specific: 16 Gy TLI treated recipients of BUF hearts rejected their grafts in a MST of 27 days when treated with third-party BN H-Ag. The state of unresponsiveness was transferable to 6 Gy total-body-irradiated WFu recipients of BUF hearts with 60 x 10(6) purified T cells isolated from TLI/H-Ag-treated rats (greater than 100) but not from normal controls (MST = 6). In vitro analysis of nontransplanted WFu rats 1-4 weeks after completion of 16 Gy TLI therapy alone demonstrated a nonspecifically reduced MLR proliferative response as well as the presence of potent nonspecific suppressor cells (NSC). By 3 or even 6 months post-TLI, W3/25- NSC displayed persistent suppressive activity and inhibited normal proliferative response to alloantigens. Limiting dilution assay revealed that the frequency of T cytotoxic cells (fTc) was severely decreased to 1:63111 at one day and to 1:16488 at one week postirradiation in comparison with normal control (1:2551). At 3 and 6 months the fTc of 1:2301 and 1:2040, respectively, approximated normal levels. These combined in vivo and in vitro results demonstrate that 16 Gy TLI therapy induces an unresponsiveness mediated by NSC and that the administration of donor type H-Ag facilitates the generation of potent regulatory T cells capable of inducing prolonged heart allograft survival.

Animals↗
PubMed1978

Enhancement of cardiac allografts in rats at the major AbG locus. I. Synergistic effect of specific and non-specific immunosuppression.

Investigations of the specific and nonspecific immunosupression of heart transplants in rats are presented. Pretreatment of the Wistar recipient of the August heart with donor strain cellular antigen and anti-donor hyperimmune serum 11 and 10 days before transplantation caused enhancement of the heart graft in this strain combination differing in the major AgB histocompatibility locus. Combination of that protocol with non-specific immunosuppression, i.e. ATS treatment caused synergistic effect. Heart grafts in animal treated with that full protocol of biological immunosuppression survived for 50.8 days.

Animals↗
PubMed1978

Active enhancement of dog kidney allografts using ALG and donor platelets.

The results of the studies indicate that platelets can be used as donor specific antigen in protocols of "biological suppression". Administration of donor specific platelets 10 days after transplantation to unmatched mongrel dogs treated for a brief period with ALG resulted in a marked prolongation of kidney allograft survival. Acute rejection of a second kidney from an indifferent donor suggests that a state of specific unresponsiveness was achieved by recipients pretreatment with ALG and donor antigen challenge.

Animals↗