Modulation of CD4 Antigen Expression on the Lymphocyte Surface by Immunosuppressive Acidic Protein in Cancer Patients

Yamaguchi, Yoshiyuki; Miyahara, Eiji; Funakoshi, Mahito; Takashima, Ikuhiro; Kawami, Hiroyuki; Satô, Yukio; Toge, Tetsuya

doi:10.1159/000227418

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…Surgical stress induces the release of cytokines such as TNF-α, IL-1, IL-6 and IL-8 from the operated site or the damaged tissues. IL-6 is the main mediator of the host acute phase responses, and stimulates hepatocytes to produce acute phase reactants such as immunosuppressive acid protein (IAP), C-reactive protein (CRP), and others [ 20 , 21 ]. IAP is reported to modulate the CD4 antigen expression by lymphocytes [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…IL-6 is the main mediator of the host acute phase responses, and stimulates hepatocytes to produce acute phase reactants such as immunosuppressive acid protein (IAP), C-reactive protein (CRP), and others [ 20 , 21 ]. IAP is reported to modulate the CD4 antigen expression by lymphocytes [ 21 ]. Therefore, the increase in IL-6 levels after small intestinal resection might be one of the factors that suppress lymphocyte function, such as CD4+ T cell depletion or a shift to Th2.…”

Section: Discussionmentioning

confidence: 99%

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Changes in Lymphocyte Phenotypes and Cytokine Production by Surgical Stress in a Rat Small Intestinal Resection Model

Murakami

Sato

et al. 2007

J. Clin. Biochem. Nutr.

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Summary Small intestinal resection rats are used widely as a malabsorption model, but the immunological changes are unclear. We examined the changes in systemic and mucosal immune status after a small intestinal resection in rats with a controlled nutritional status. Rats had 60% of their small intestine removed. At 5 days after the surgery, spleen cells and intraepithelial lymphocytes (IEL) were isolated. The phenotypes of spleen cells and IEL, the production patterns of Th1 and Th2 cytokines, and the proinflammatory cytokine levels in the plasma were measured. CD4+ T cells in the blood and spleen were significantly decreased in the Resection group (p<0.05). In contrast, IEL subpopulations were not different between the two groups. Interferon-γ production from the spleen cells was significantly decreased in the Resection group (p<0.05). Interleukin (IL)-4 production was not different between the two groups. Plasma IL-6 concentrations were significantly elevated in the Resection group 6 h after surgery (p<0.05). In conclusions, small intestinal resection in rats suppressed systemic immunity, and this model is useful as a surgical stress model.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Changes in Lymphocyte Phenotypes and Cytokine Production by Surgical Stress in a Rat Small Intestinal Resection Model

Murakami

Sato

et al. 2007

J. Clin. Biochem. Nutr.

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“…IAP has been reported to be a member of the ·1-acid glycoprotein family (19). IAP also has been demonstrated to down-modulate CD4 molecules on the lymphocyte surface, leading to the establishment of cancer-associated immunodepression, and to induce suppressor-inducer cells (20). Con-A-induced suppressor cell activity has been reported to indicate the presence of suppressor precursor cells that mature in response to stimulation with suppressor inducer cells (17).…”

Section: Discussionmentioning

confidence: 99%

Postoperative immunosuppression cascade and immunotherapy using lymphokine-activated killer cells for patients with esophageal cancer: Possible application for compensatory anti-inflammatory response syndrome

Yamaguchi

Hihara²,

Hironaka³

et al. 2006

Oncol Rep

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Abstract.Immunological parameters were measured in order to elucidate a postoperative immunosuppression mechanism in transthoracic esophagectomy for patients with esophageal cancer. Moreover, lymphokine-activated killer (LAK) cells were transferred just after the surgery to overcome the postoperative immunosuppression. Fifteen consecutive patients who underwent transthoracic esophagectomy were subjected to the postoperative measurement of immunological parameters. Ten patients who underwent open cholecystectomy served as controls. Heparinized venous blood was obtained pre-and postoperatively, and serum levels of cytokines IL-6 and IL-10 and immunosuppressive acidic protein (IAP) were measured. Peripheral blood lymphocytes were harvested and analyzed by flow cytometry for phenotype detection and by a mixed lymphocyte reaction for detecting concanavalin (Con)-A-induced or -non-induced suppressor activity. Another 29 consecutive patients who underwent transthoracic esophagectomy were randomly enrolled in a postoperative immunotherapy trial either with or without lymphokineactivated killer cells. It was found that, in the esophagectomy group, IL-6 and IL-10 increased postoperatively and peaked on day 1, followed by an increase in IAP, peaked again on day 4, with a profound decrease in helper and cytotoxic T-cell subsets, followed by increases in Con-A-induced (on day 7 or later) and spontaneous (on day 10) suppressor activities. These changes were minimal in the cholecystectomy group. LAK cell transfer restored the postoperative decrease in the helper and cytotoxic T-cell population, and there was a trend of reduction for postoperative remote infection such as pneumonia and surgical site infection in the LAK therapy group. Taken together, we would like to propose the existence of a postoperative immunosuppression cascade consisting of increases in cytokines and immunosuppressive proteins, decreases in helper and cytotoxic T-cell populations, and the development of suppressor T-cell activities in surgery for esophageal cancer. Postoperative adoptive transfer of LAK cells may be a novel clinical application in surgery for esophageal cancer as a means of treating this postoperative immunosuppressive condition that may be identical to the status of compensatory anti-inflammatory response syndrome (CARS).

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“…IAP has been shown to impair phytohemagglutinininduced lymphocyte blastogenesis and the 2-way mixedlymphocyte reaction (Tamura et af., 1981). The induction of suppressor macrophages by IAP was demonstrated in mice, and it has been shown that IAP leads to down-modulation of CD4 antigen on human lymphocytes (Yamaguchi et al, 1995).…”

mentioning

confidence: 99%

Circulating immunostimulatory protein 90K and soluble interleukin-2-receptor in human ovarian cancer

et al. 1996

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The tumor-associated antigen 90K is thought to play an important role in cellular immune defense against malignant cells. It is therefore of interest to investigate whether circulating 90K could be used as a prognostic variable in ovarian cancer, and whether this immunostimulatory antigen is related to other parameters known to be involved in the cellular immune response. In the present retrospective study, circulating levels of antigen 90K were measured before primary surgery in 152 ovarian-cancer patients. A very close association between antigen 90K and s-IL-2R concentrations was pointed out in a stepwise logistic regression model. Univariate analysis of overall survival revealed that antigen 90K and s-IL-2R were associated with poor prognosis. In the multivariate Cox regression, however, neither antigen 90K nor s-IL-2R retained independent prognostic significance. Urinary neopterin was shown to be the only independent prognostic variable among the "immunological parameters" investigated. Additionally, residual disease after primary tumor debulking and histopathologic tumor grade were the most prominent clinico-pathologic parameters for the independent prediction of poor clinical outcome in ovarian-cancer patients.

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Modulation of CD4 Antigen Expression on the Lymphocyte Surface by Immunosuppressive Acidic Protein in Cancer Patients

Cited by 7 publications

References 8 publications

Changes in Lymphocyte Phenotypes and Cytokine Production by Surgical Stress in a Rat Small Intestinal Resection Model

Changes in Lymphocyte Phenotypes and Cytokine Production by Surgical Stress in a Rat Small Intestinal Resection Model

Postoperative immunosuppression cascade and immunotherapy using lymphokine-activated killer cells for patients with esophageal cancer: Possible application for compensatory anti-inflammatory response syndrome

Circulating immunostimulatory protein 90K and soluble interleukin-2-receptor in human ovarian cancer

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