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Biomedical subjects

R Hintermeier-Knabe

Publications and source records attributed to R Hintermeier-Knabe.

6 recordsLinked to original sources
PubMed2000

Prognostic significance of increased IL-10 production in patients prior to allogeneic bone marrow transplantation.

IL-10 is a potent immunosuppressant which inhibits allo-antigen-specific T cell responses. In addition, IL-10 is a strong endogenous anti-inflammatory cytokine. To investigate the role of IL-10 in the induction of acute GVHD following allogeneic bone marrow transplantation (BMT) we performed a prospective study on spontaneous IL-10 production by peripheral blood mononuclear cells (PBMNC) in 84 patients admitted for allogeneic BMT. High spontaneous IL-10 production by PBMNC at the time of admission and prior to any preparative treatment correlated with a subsequent low incidence of GVHD and transplant-related mortality (8%), as compared to patients with low or intermediate IL-10 production (50%, P < 0. 01). Our data demonstrate the prognostic significance of increased IL-10 production in BMT patients and suggest a major role of IL-10 in maintaining immunobalance in the setting of allogeneic BMT. Bone Marrow Transplantation (2000) 25, 237-241.

Adolescent↗
PubMed1997

Inflammatory reactions induced by pretransplant conditioning--an alternative target for modulation of acute GvHD and complications following allogeneic bone marrow transplantation?

Intensity of pretransplant conditioning has been closely correlated with regimen related toxicity in patients receiving allogeneic bone marrow transplantation (BMT). In this review, we summarize evidence for a direct link between inflammatory reactions induced by irradiation and cytotoxic treatment and occurrence of acute graft-versus-host disease (GvHD) as well as endothelial complications: In our studies, de novo release of TNFalpha during conditioning was associated with an increased risk of severe GvHD and mortality following BMT, whereas increased spontaneous production of IL-10, an endogenous TNF-antagonist, prior to conditioning protected from these complications. Immunogenetic differences in cytokine regulation and costimulation by endotoxin proved to be important cofactors determining the extent of inflammatory cytokine release in individual patients. Pathophysiological relevance of these findings seems to be confirmed by experimental as well as first clinical trials using TNF-antibodies and related antagonists during pretransplant conditioning. Preclinical experiments suggest additional, cytokine independent inflammatory reactions induced by irradiation such as expression of ICAM-1 and endothelial cell apoptosis. Although the exact impact of these findings on pathophysiology of BMT related complications needs further clarification by future studies, conditioning related inflammation as a first crucial step in induction of GvHD and complications has to be considered when designing new protocols for preparation of patients for allogeneic BMT.

Animals↗
PubMed1995

Modulation of acute graft-versus-host-disease after allogeneic bone marrow transplantation by tumor necrosis factor alpha (TNF alpha) release in the course of pretransplant conditioning: role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human TNF alpha (MAK 195F).

Contribution of host-related cytokine release in the course of pretransplant conditioning to early tissue damage and induction of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) has been shown in experimental models. We performed a clinical phase I/II trial applying a monoclonal antibody neutralizing human tumor necrosis alpha (TNF alpha) during pretransplant conditioning as additional prophylaxis in high-risk patients admitted to allogeneic BMT; TNF alpha serum levels and clinical courses in 21 patients receiving anti-TNF alpha prophylaxis were compared with data from 22 historical controls. Absence of significant release of TNF alpha in the period of busulphan (BUS) treatment, but significant induction of TNF alpha by total body irradiation (TBI) and cyclophosphamide (CY) conditioning were correlated with significantly earlier onset of acute GVHD in patients receiving TBI/CY regimens as compared with BUS/CY-treated patients. Prophylactic application of monoclonal anti-TNF alpha seemed to postpone onset of acute GVHD from day 15 to day 25 (P < .05) after TBI/CY and from day 33 to day 53 after BUS/CY (P < .10) conditioning. Application of monoclonal anti-TNF alpha in low and intermediate doses was safe and not associated with an increased incidence of infectious or hematologic complications. Thus, our data provide indirect and direct evidence for involvement of conditioning-related cytokine release in induction of early acute GVHD in the clinical setting and support further investigation of this novel approach in randomized trials.

Acute Disease↗
PubMed1994

Ionizing radiation induces human intercellular adhesion molecule-1 in vitro.

Intercellular adhesion molecule-1 (ICAM-1) plays a central role in various inflammatory reactions and its expression is readily induced by inflammatory stimuli such as cytokines or ultraviolet irradiation. We have investigated the effect of ionizing radiation (IR) on human ICAM-1 expression in human cell lines and skin cultures. ICAM-1 mRNA levels in HL60, HaCaT, and HeLa cells were elevated at 3-6 h after irradiation and increased with doses from 10-40 Gy. The rapid induction of ICAM-1 occurred at the level of transcription, was independent of de novo protein synthesis, and did not involve autocrine stimuli including tumor necrosis factor-alpha and interleukin-1. IR also induced ICAM-1 cell surface expression within 24 h. Immunohistologic analysis of cultured human split skin revealed ICAM-1 upregulation on epidermal keratinocytes and dermal microvascular endothelial cells 24 h after exposure to 6 Gy. In conclusion, we propose ICAM-1 as an important radiation-induced enhancer of immunologic cell adhesion, which contributes to inflammatory reactions after local and total body irradiation.

Antibodies↗
PubMed1991

Low incidence of transplant-related complications in patients with chronic release of tumor necrosis factor-alpha before admission to bone marrow transplantation: a clinical correlate of cytokine desensitization?

To investigate the role of tumor necrosis factor-alpha (TNF-alpha) released by activated macrophages, sequential serum samples of 120 patients undergoing bone marrow transplantation (BMT) were analyzed by enzyme-linked immunosorbent assay. De novo increases in serum TNF-alpha levels were correlated with the development of acute endothelial complications as well as acute graft-versus-host disease. In addition, the analysis of time courses revealed a different capacity of TNF-alpha regulation at various phases of BMT. While patients with acute TNF-alpha release in the first 2 weeks of BMT had a significantly enhanced incidence of complications, a subgroup of 9 patients with chronic asymptomatic release of TNF-alpha before admission to BMT was observed. These patients were protected from complications in the course of the first 6 months of BMT. Our observations indicate the occurrence of desensitization for TNF-alpha, as it is also reported after repeated injections of TNF-alpha or endotoxin in experimental models.

Adolescent↗