Administration Of PSK Research Articles

Immunomodulating effect of Polysaccharide Krestin from cariolus versicolor grown in Indonesia against Rheumatoid arthritis in rat

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can lead to joint destruction, deformity, and loss of function. The aim of this study is to investigate the therapeutic effect of polysaccharides krestin from Cariolus versicolor grown in Indonesia against complete Freund's adjuvant arthritis rat. Sixty-six male Wistar white rats (Rattus norvegicus) were induced by adjuvant arthritis. Samples were divided into 6 groups, 3 control (KP1, KP2, KP3) and 3 treatment groups (KP4, KP5, KP6). There were 3 different times of data collection: 1 week, 2 weeks, and 3 weeks after booster administration. Intragastric injection of polysaccharides krestin was given at a dose of 50 mg/kg body weight per day in all treatment groups. Flowcytometry blood tests were performed to examine the TGF-β1 level and T regulator percentage. The joint scale was observed using Elisa and histopathological analysis. The analysis of various arthritic assessment parameters used in this study revealed that polysaccharides krestin from Cariolus versicolor has a considerable effect in preventing the inflammation and severe damage in adjuvant arthritis rat's joint. The correlation between polysaccharides krestin-TGF-β1, levels-CD4+CD25+FoxP3+ Treg cells expression, and histopathological joint scale during the second weeks showed a strong correlation (p ≤0.05). These findings suggest that the administration of PSK from C. versicolor appears to be promising as immunomodulator and medication in chronic arthritis, therefore preclinical and clinical studies in human are highly recommended.

Abstract 1796: The impact of adjuvant immunochemotherapy using protein-bound polysaccharide-K on overall survival of gastric cancer

Abstract Protein-bound polysaccharide (PSK) has been approved as an anti-cancer agent to be used in combination with chemotherapeutic drug for adjuvant therapy against gastric cancer. Several clinical studies have demonstrated that PSK has antitumor and immunomodulating properties. However, there is little evidence about the effectiveness of PSK in clinical practice. The aim of this study was to evaluate the impact of PSK on overall survival of patients with gastric cancer and predict the suitable case selection for postoperative adjuvant immunochemotherapy. The patients with stage II/III gastric cancer who underwent surgical curative resection between 2000 and 2007 at Deptarment of Surgical Oncology, Osaka City University were included in this retrospective study. All patients received oral fluorinated pyrimidine anti-metabolites with or without PSK after surgical operation. We analyzed clinicopathological features and evaluated the impact of PSK on postoperative survival rate of resectable gastric cancer. We identified 254 patients with a median follow-up of 33 months (range, 7-110 months). 138 patients received oral anti-metabolized alone (control group) and 115 patients received anti-metabolites plus PSK (PSK group). 139 patients of the cohort experienced postoperative recurrence. No significant difference between control and PSK group in overall survival or relapse free survival was detected over the 8-year period. In patients with early tumor recurrence, PSK group increased overall survival significantly (p<0.023). Among patients with pN3 lymph nodes metastasis, PSK group had better median overall survival of 28 months compared with 22 months with oral chemotherapeutics alone. After multivariate Cox regression analysis, duration of PSK administration was associated with an increased overall survival (p=0.002, HR 0.964, 95%CI 0.942 to 0.987). Our results suggested that adjuvant immunochemotherapy with PSK increased overall survival for patients with pN3 and early tumor recurrence. A population with lymph nodes metastasis might be a suitable to combine PSK with oral chemotherapeutic agents for postoperative adjuvant therapy against gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1796. doi:10.1158/1538-7445.AM2011-1796

Involvement of Phytosulfokine in the Attenuation of Stress Response during the Transdifferentiation of Zinnia Mesophyll Cells into Tracheary Elements

Phytosulfokine (PSK) is a sulfated peptide hormone required for the proliferation and differentiation of plant cells. Here, we characterize the physiological roles of PSK in transdifferentiation of isolated mesophyll cells of zinnia (Zinnia elegans 'Canary Bird') into tracheary elements (TEs). Transcripts for a zinnia PSK precursor gene, ZePSK1, show two peaks of expression during TE differentiation; the first accumulation is transiently induced in response to wounding at 24 h of culture, and the second accumulation is induced in the final stage of TE differentiation and is dependent on endogenous brassinosteroids. Chlorate, a potent inhibitor of peptide sulfation, is successfully applied as an inhibitor of PSK action. Chlorate significantly suppresses TE differentiation. The chlorate-induced suppression of TE differentiation is overcome by exogenously applied PSK. In the presence of chlorate, expression of stress-related genes for proteinase inhibitors and a pathogenesis-related protein is enhanced and changed from a transient to a continuous pattern. On the contrary, administration of PSK significantly reduces the accumulation of transcripts for the stress-related genes. Even in the absence of auxin and cytokinin, addition of PSK suppresses stress-related gene expression. Microarray analysis reveals 66 genes down-regulated and 42 genes up-regulated in the presence of PSK. The large majority of down-regulated genes show significant similarity to various families of stress-related proteins, including chitinases, phenylpropanoid biosynthesis enzymes, 1-aminocyclopropane-1-carboxylic acid synthase, and receptor-like protein kinases. These results suggest the involvement of PSK in the attenuation of stress response and healing of wound-activated cells during the early stage of TE differentiation.

PROTECTIVE EFFECT OF A PROTEIN-BOUND POLYSACCHARIDE, PSK, ON CLP-INDUCED SEPSIS IN MICE TRANSPLANTED ORTHOTOPICALLY WITH COLON TUMOR

We investigated the effects of a protein-bound polysaccharide, PSK, on the resistance of tumor-bearing mice against sepsis induced by cecal ligation and puncture (CLP). (a) In BALB/c mice that had received intracecal transplantation of colon 26 (C26) tumor, CLP with a 21-gauge needle significantly shortened the survival time, compared with that of non-tumor-bearing mice. Oral administration of PSK to such mice resulted in a significant prolongation of the survival time and increase of the survival rates. The effects were dependent on the timing of PSK administration and the dose. (b) CLP significantly increased the IL-10 level in serum, the IL-10 gene expression by spleen cells, the number of IL-10-producing CD4-positive T cells, and the productivity of IL-10 by spleen of tumor-bearing mice compared with that of non-tumor-bearing mice. PSK administration to such mice suppressed the increase. Further, PSK prevented the reduction of gene expression of IFN-gamma and the number of IFN-gamma-producing CD4-positive T cells and IFN-gamma productivity by spleen cells of tumor-bearing CLP-treated mice. (c) Treatment with anti-IFN-gamma monoclonal antibody before CLP significantly reduced the effects of PSK. These findings suggest that the protective effect of PSK on the CLP-induced sepsis in mice transplanted orthotopically with C26 tumor is possibly mediated by suppression of IL-10 and promotion of IFN-gamma.

Protective effects of a protein-bound polysaccharide, PSK, against Candida albicans infection in syngeneic tumor-bearing mice via Th1 cell functions.

We investigated the effects of a protein-bound polysaccharide, PSK, on the resistance of tumor-bearing mice against Candida albicans infection. In BALB/c mice that had received subcutaneous (sc) transplantation of fibrosarcoma Meth A, viable fungal counts were increased in the kidney and the mean survival period was shortened after challenge with C. albicans, compared with healthy mice. Oral administration of PSK to such mice resulted in a significant decrease of viable fungal counts and a prolongation of the mean survival period. The ratio of CD4-positive T cells in the spleen was decreased in noninfected tumor-bearing mice and the decrease was prevented by PSK, although in vitro anticandida activities of phagocytes were not significantly affected by tumor burden or PSK. Further, intracellular interferon (IFN)-gamma productivity was enhanced and the number of IFN-gamma-producing CD4-positive T cells was enhanced by PSK. PSK enhanced the gene expression of interleukin (IL)-12 and IFN-gamma in the spleen of tumor-bearing mice inoculated with C. albicans. Treatments with anti-IL-12 or anti-IFN-gamma antibody reduced the anti-infectious effects of PSK. These findings suggest that the protective effect of PSK on sublethal inoculation with C. albicans in tumor-bearing mice is possibly mediated by Th1 cell functions.

Protective effects of a protein-bound polysaccharide, PSK, on Candida albicans infection in mice via tumor necrosis factor-α induction

We investigated the protective mechanism of a protein-bound polysaccharide, PSK, against lethal infection with Candida albicans ( C. albicans) in mice. (1) In BALB/c mice inoculated intravenously with C. albicans, the intraperitoneal (ip) administration of PSK increased survival rates and prolonged the survival period depending on the time of administration, the dosage, and the size of fungal inoculum; the maximal effect was obtained when PSK 250 mg/kg was ip administered to mice 24 h before inoculation of 1×10 6 C. albicans (30 days survivors showed 60% and the mean survival period of mice with fatal infection increased 209%). (2) The protective effect of PSK was significantly decreased in mice treated with cyclophosphamide or carrageenan, or in mice treated previously with anti-tumor necrosis factor-α (TNF-α) antibody. (3) The administration of PSK significantly enhanced the expression of TNF-α gene in spleen and increased leukocyte functions from 6 h to 1 day after inoculation. (4) When the PSK fraction subjected to hydrolysis with β1–3 glucanase or hydrazine was used instead of PSK, the anti-fungal activities were significantly decreased. These findings suggested that the protective effect of PSK on lethal C. albicans infection in mice was mainly produced via TNF-α functions, and that β1–3 glucan and protein moiety in PSK molecule were involved in the expression of the activities.

Gut Bacterial Translocation during Total Parenteral Nutrition in Experimental Rats and Its Countermeasure

Background: The use of total parenteral nutrition (TPN) is commonly associated with mucosal lining of the intestinal tract, causing degenerative changes within the gut-associated lymphoid tissue (GALT). These phenomena are probably caused by the translocation of indigenous intestinal bacteria into other organs and tissues where they induce infections. Methods: Using TPN model rats, this paper looks at the result of the investigation of the action of PSK (proteoglycan), a biological response modifier, which appears to suppress bacterial translocation and maintain local immunity activity. Results: Culture of mesenteric lymph nodes obtained post-TPN demonstrate a bacterial rate as high as 60%. Immunohistochemical examination indicates a reduction in the number of plasma cells and a decrease in S-IgA production and secretion. A similar reduction in S-IgA within bile and portal venous blood was also confirmed. Continuous oral administration of PSK in a daily dose of 1,000 mg/kg had a protective effect against the degeneration of GALT. A staining in immunocytes of Peyer’s patches using immunohistochemical study was performed after administration of PSK and revealed constant levels of MHC-I, MHC-II, T helper cells, and interleukin-2 producing cells, supporting the protective role of PSK against degeneration of GALT with a subsequent reduction in bacterial translocation. Conclusions: Proteoglycan can restore the impaired local immunity in the intestinal tract to normal levels and suppression of the bacterial translocation to provide an important function for patients receiving TPN treatment.

Oral administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice.

We investigated both the effect and the mechanism of oral (p.o.) administration of PSK, a protein-bound polysaccharide derived from Basidiomycetes, on the anti-tumor T-cell response in gut-associated lymphoid tissue (GALT). The p.o. administration of PSK significantly suppressed the growth of colon 26 carcinoma (C-26) inoculated into the subserosal space of the cecum (i.c.), and augmented the tumor-neutralizing activity of the draining mesenteric lymph node (LN) cells. PSK treatment also significantly decreased the levels of immunosuppressive factors such as plasma transforming growth factor (TGF)-beta in the i.c. C-26-inoculated mice. We also evaluated the improving effect of PSK on the anti-tumor T-cell response in GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The PSK treatment promoted the rejection of i.c.-inoculated B7/P815 and restored the CD4+ T-cell-dependent proliferative response of the draining mesenteric LN cells against in vitro restimulation. Furthermore, the treatment also decreased the TGF-beta production but increased the IFN-gamma production of these cells. The p.o. administration of PSK, however, showed no effect in the CD8+ T-cell-dependent cytolytic activity of the draining mesenteric LN cells after in vitro restimulation. Overall, these results indicate that the p.o. administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in GALT, mainly through a suppression of TGF-beta production and a restoration of IFN-gamma production.

Oral administration of psk can improve the impaired anti‐tumor CD4 T‐cell response in gut‐associated lymphoid tissue (GALT) of specific‐pathogen‐free mice

Oral administration of psk can improve the impaired anti‐tumor CD4 T‐cell response in gut‐associated lymphoid tissue (GALT) of specific‐pathogen‐free mice

Enhanced resistance against Edwardsiella tarda infection in tilapia ( Oreochromis niloticus) by administration of protein-bound polysaccharide

A protein-bound polysaccharide preparation, PS-K, isolated from Coriolus versicolor was evaluated for its ability to enhance resistance against Edwardsiella tarda, causal agent of classical edwardsiellosis in tilapia, Oreochromis niloticus. At a dose rate of 0.1 mg PS-K g −1 body weight, maximal resistance was developed in fish 1 week after intraperitoneal injection. Enhanced resistance was first observed at 3 days and maintained for 21 days post-injection. Furthermore, oral administration of PS-K (0.1 mg g −1 body weight) to fish daily for 21 days prior to an intraperitoneal challenge with E. tarda resulted in enhanced resistance, manifested as reduced mortality relative to controls. Intraperitoneal administration of PS-K 24 h after challenge with E. tarda also enhanced resistance and demonstrates the potential of PS-K as a prophylactic agent in aquaculture. In PS-K injected fish, increased phagocytic activity of pronephros cells against sheep red blood cells and rapid elimination of the bacteria from the blood and liver suggested that PS-K enhanced the resistance of tilapia to bacterial infection through the activation of the nonspecific immune system.

Antitumor effect of the angiogenesis inhibitor TNP-470 and its combination effect with 5-FU and PSK in colon 26 tumors

TNP-470 is known to inhibit angiogenesis. In this study, we investigated the antitumor effect of TNP-470 in colon 26 tumors. A dose dependent growth inhibition of tumor and liver metastasis was observed. An additive administration of PSK enhanced inhibitory effect of the tumor. Combined treatment of TNP-470 and 5-FU significantly prolonged the life span compared to the TNP-470 and 5-FU group. It is suggested that the combination of TNP-470 and 5-FU might be effective for the treatment of colon cancer and PSK might increase the antitumor effect from the viewpoint of immunity and angiogenetic mechanism.

Induction of gene expression for immunomodulating cytokines in peripheral blood mononuclear cells in response to orally administered PSK, an immunomodulating protein-bound polysaccharide.

The protein-bound polysaccharide extracted from a fungus, PSK, has been used as a biological response modifier in the treatment of cancer patients in Japan for over 16 years. The administration of PSK to tumor-bearing rodents inhibited tumor growth and modulated immune responses. Recently, an in vitro study has revealed that PSK is a strong inducer of cytokine gene expression and production in human peripheral blood mononuclear cells (PBMC). To establish whether PSK has cytokine-inducing activities in vivo, we have orally administered PSK (1 g, the clinical dose) to 12 healthy volunteers and 9 gastric cancer patients who had undergone gastrectomy, and assessed the gene expression for cytokines in PBMC of each subject. As determined by the reverse-transcribed polymerase chain reaction method, the induction of gene expression for both tumor necrosis factor alpha and interleukin-8 (IL-8) was detected in PBMC from 5 of the 12 healthy volunteers (42%) and 4 of the 9 patients (44%). Furthermore, the concentration of serum IL-8 was elevated in 5 healthy volunteers given PSK orally, who had shown induction of IL-8 gene expression, as detected by enzyme-linked immunosorbent assay. These findings indicate that responsiveness of PBMC to PSK, in terms of gene expression and production of cytokines, varies among individuals. Thus, when using PSK to treat cancer patients, it seems advisable to select patients on the basis of their responsiveness to PSK. We speculate that the cytokines induced by PSK might mediate the immunoenhancing action of this agent in vivo.

ヒト胃癌におけるPyNPase活性に及ぼすPSK腫瘍内投与の影響

ヒト胃癌におけるPyNPase活性に及ぼすPSK腫瘍内投与の影響

An in vivo Study of Hepatic and Splenic Interleukin‐lβ mRNA Expression Following Oral PSK or LEM Administration

The effects of orally administered biological response modifiers (BRMs) in preventing postoperative micro liver metastasis of primary colorectal cancer were examined in experimental animals. The twoBRMs tested were Krestin (PSK) and Lentinus edodes mycelia (LEM). In previous experiments, we found that oral administration of PSK or LEM suppressed liver metastasis and prolonged the survival period. We also found that these agents elevated the liver natural killer (NK) and liver macrophage activities. In the present study in vivo, using reverse transcriptase‐polymerase chain reaction (RT‐PCR), we examined whether or not the liver and spleen have cytokines which would induce NK cells and macrophages, and whether or not the liver and spleen have cytokines induced by NK cells or macrophages. We placed emphasis on the examination of interleukin (IL)‐1β expression in the liver and spleen in vivo. Two to six hours after oral administration of PSK or LEM (1 g/kg) to mice, IL‐β levels in the liver and spleen rose, and they returned to their baseline levels 24 h later. These findings suggest two possibilities: (1) hepatic IL‐1β is potentiated by these agents soon after administration, resulting in activation of liver NK cells or macrophages, or (2) these agents stimulate IL‐β production by liver macrophages, and the produced IL‐lβ activates liver NK cells or liver macrophages (Kupffer cells). The results of this in vivo study suggest that the potentiation of hepatic and splenic IL‐β by PSK and LEM is involved in the early phases of suppression of micro liver metastases of colorectal cancer.

Suppression of hepatic natural killer activity by liver metastasis of cancer and restoration of killer activity by oral administration of a Basidomycetes-derived polysaccharide, PSK.

PSK (Krestin) is a protein-bound polysaccharide with antitumor and immunomodulatory activity. In this study, the effects of the oral administration of PSK were investigated on the natural killer (NK) activity of liver-associated lymphocytes and their subfractions separated by density gradient centrifugation, in WKAH rats with liver metastasis of KDA hepatoma. PSK was administered orally, at a dose of 500 mg/kg once a day for 3 weeks. The NK activity of nonparenchymal liver cells (NPLC) and their subfractions, including large granular lymphocytes (LGL), was markedly augmented by this treatment. The effects of oral PSK were also examined in CDF1 mice with liver metastases of Colon 26 adenocarcinoma; the survival of tumor-bearing mice was prolonged and both metastatic foci and liver weight were decreased. These results suggest that PSK may be effective for the suppression of liver metastasis through activation of liver-associated NK cells.

Enhancement of antitumor cytotoxicity of hepatic lymphocytes by oral administration of PSK.

We have studied the effects of oral administration of a biological response modifier (BRM), PSK, on hepatic lymphocytes. Many PSK positive cells were observed in the liver by anti-PSK antibody staining. Flow cytometric analysis revealed an increase in the number of OX8 (CD8) positive cells in the non-parenchymal nonadherent liver cells (NPNALCs) which were isolated from the liver enzymatically digested by perfusion with collagenase. NPNALCs were fractionated by discontinuous density gradient centrifugation, and the number and cytotoxic activity of these cells were examined in each fraction. Although the yield of lymphocytes in each fraction was not significantly increased by the oral administration of PSK, the natural killer (NK) activity was markedly enhanced in low density fractions. The present findings suggest that oral administration of PSK is effective for prevention of liver metastasis through the augmentation of organ-associated NK activity.

Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on cytotoxicity of PSK-induced peritoneal polymorphonuclear leukocytes (PMNs).

We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced the cytotoxicity of PSK-induced polymorphonuclear leukocytes (PMNs) in the peritoneal cavity. Male C3H/He mice, 8- to 10-week-old, received single subcutaneous (s.c.) or intraperitoneal (i.p.) injection of 2.5 micrograms/animal of rhG-CSF at different time points before or after an i.p. administration of PSK. In other experiments, mice were s.c. or i.p. treated with the same dosage of rhG-CSF every day for 7 or 14 consecutive days and i.p. injected with 2.5 mg/animal of PSK on the last day. Peritoneal PMNs were harvested 6 hrs after the administration of PSK and purified to more than 95% by Ficoll-Paque for in vitro cytotoxic assay. In vitro cytotoxic assays with 51Cr labeled MM46 mammary carcinoma cells were added with 5-20 micrograms/ml of Nocardia rubra cell wall skeleton (N-CWS) at the beginning of the assay to augment the cytotoxic activity of PMNs. In vitro addition of rhG-CSF to the assay did not enhance the cytotoxicity of PSK-induced PMNs. However, the cytotoxicity was significantly increased when rhG-CSF was s.c. administered 12 hrs before a PSK injection or 2 or 5 hrs after that. On the other hand, the cytotoxicity was rather weak when mice s.c. or i.p. received consecutive injections of rhG-CSF. This cytotoxicity may be mediated by H2O2, since H2O2 production of PMNs during the cytotoxic assay appears to correlate with the levels of cytotoxicity under suppressed H2O2 generation by catalase or enhanced generation by rhG-CSF. These results suggest that rhG-CSF augments the cytotoxicity of PSK-induced PMNs when administered in vivo timely.

Antitumor effect of PSK at a distant site: tumor-specific immunity and combination with other chemotherapeutic agents.

The antitumor effect of PSK, a Coriolus preparation, was analyzed with the double grafted tumor system in which BALB/c mice received intradermal inoculations of syngeneic Meth‐A fibrosarcoma in the right (primary tumor, 105 cells) and left (distant tumor, 2 × 105 cells) flanks. Intratumoral administration of PSK significantly inhibited the growth of not only the right but also the left tumor. PSK also inhibited the growth of a methylcholanthrene‐induced fibrosarcoma BAMC‐1, and a methylurethane‐induced adenocarcinoma Colon 26 in the double grafted tumor system of syngeneic BALB/c mice. However, when the left distant tumor was different from the right Meth‐A tumor, the intratumoral administration of PSK in the right tumor was unable to inhibit the growth of the left’ BAMC‐1 or RL♂ ‐1 tumor. The PSK‐induced immunity, therefore, is tumor‐specific and T lymphocytes may play an important role in antitumor memory function. The enhancement of concomitant immunity by PSK treatment was completely impaired by previous intravenous administration of an alkylating agent, cyclophosphamide (CY). The enhancement of sinecomitant immunity by PSK treatment was also impaired by previous CY intravenous administration. The antitumor effect of PSK was suppressed by previous intravenous administration of another alkylating agent, ACNU. It is possible that alkylating agents suppress the function of effector T cells and granulocytes which are very important for the antitumor immune cascade reaction due to PSK treatment. On the other hand, the antitumor effect of PSK was enhanced by previous intravenous administration of an anti‐metabolite, 5‐fluorouraeil.

Effect of Krestin<sup>R</sup> (PSK) on the Induction of IL-2 Activated Killer Cells

The effects of Krestin (PSK) on the generation of lymphokine-activated killer (LAK) cells were examined in tumor-bearing mice. BALB/c mice were inoculated subcutaneously with methylcholanthrene-induced fibrosarcoma (Meth A) cells, and PSK was administered intraperitoneally every other day. The reduced LAK activity in tumor-bearing mice was restored by the administration of PSK. Since involvement of the humoral immunosuppressive factor in the impairment of LAK activity has been suggested, the effect of PSK on the impaired LAK activity in the presence of an immunosuppressive factor isolated from the ascites of X5563 (plasmacytoma)-inoculated mice was examined. The activity reduced by the immunosuppressive factor in an in vitro induction of LAK was restored by incubation with PSK. The antimetastatic effect of IL-2 was also augmented by its combined use with PSK. The data provide a rational basis for using PSK in combination with recombinant IL-2 in cancer immunotherapy.

Activation of human natural killer cells by the protein-bound polysaccharide PSK independently of interferon and interleukin 2.

The protein-bound polysaccharide PSK was tested for the ability to activate human natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16+ large granular lymphocytes (LGL) were treated in vitro overnight with PSK, they demonstrated enhanced NK cell activity against K562. The PSK-activated killer cells also lysed NK-resistant targets and freshly isolated autologous and allogeneic tumor cells. The PSK effect was observed with concentrations that could be obtained in the blood of cancer patients receiving oral administration of PSK. PSK-induced enhancement of NK activity was not abrogated by monoclonal antibodies (mAb) that neutralized interferon (IFN) alpha, IFN gamma, or interleukin-2 (IL-2). In addition, mAb reactive with p55 (alpha chain) or p75 (beta chain) glycoproteins of IL-2 receptors had no effects on PSK-enhanced NK activity even when used simultaneously. These results indicate that the PSK could activate human NK cells independently of IFN and IL-2/IL-2R systems.