化疗联合胸腺肽α1治疗乳腺癌的基础与临床观察

目的评价观察化疗联合胸腺肽α1对乳腺癌患者毒副作用及免疫功能的影响。方法87例乳腺癌患者随机分为治疗组43例和对照组44例。对照组单用化疗。治疗组采用胸腺肽α1＋化疗,胸腺肽α1给药方案：化疗当天开始1．6mg／周,皮下注射,直至患者完成2个疗程的化疗。结果2组均按期完成化疗计划。化疗期间,治疗组19例,对照组有31例WBC〈4×10^9／L。2组WBC〈4×10^9／L患者的例数差异有统计学意义（x^2=6．14,P〈0．05）。对照组有26例患者,治疗组有34例出现胃肠道不良反应。2组胃肠道不良反应发生率差异有统计学意义（x^2=4．06,P〈0．05）。治疗组化疗后细胞免疫指标水平高于对照组,差异有统计学意义（P〈0．05或P〈0．01）。结论胸腺肽α1配合化疗能提高患者的免疫功能,改善患者生活质量。     

Activation of tumor-associated macrophages by thymosin alpha 1

It was shown earlier that the progressive growth of a transplantable T-cell lymphoma of spontaneous origin, designated as Dalton's lymphoma (DL), in a murine host is associated with an inhibition of macrophages (TAM) along with an involution of thymus. However, it remained unclear if a decline in the level of thymic peptides in DL-bearing host, due to thymic regression, has any implications in the inhibited responses of TAM. Therefore, the present investigation was under taken to study whether the TAM of DL-bearing host can be activated to tumoricidal state by peptides of thymic origin. It was observed that intraperitoneal administration of thymosin alpha 1 to DL-bearing mice resulted in activation of TAM. Such TAM were found to produce enhanced amount of interleukin-1 (IL-1), tumor necrosis factor (TNF), reactive oxygen intermediates (ROI), nitric oxide (NO) and showed an increased abilities of pinocytosis, phagocytosis, antigen presentation and tumor cytotoxicity. The TAM were found to be directly responsive to thymosin alpha1 as in vitro treatment with thymosin alpha 1 could activate TAM to tumoricidal state. Treatment of TAM with thymosin alpha 1 also enhanced their LPS responsiveness for an augmented state of activation. The findings of this study demonstrate for the first time that the TAM of a T cell lymphoma can be activated to tumoricidal state by thymosin alpha 1.     

胸腺肽α1治疗老年慢性阻塞性肺病急性发作期的疗效观察

目的探讨胸腺肽α1治疗老年慢性阻塞性肺病(COPD)急性发作期的疗效。方法将54例老年COPD急性期住院患者随机分为常规治疗组和胸腺肽治疗组2组,胸腺肽治疗组在常规治疗组基础上加用胸腺肽α11.6mg皮下注射,1次/d,疗程2周。观察2组患者血清C反应蛋白(CRP)和降钙素原(PCT)水平、细胞免疫功能水平和临床疗效。结果治疗后胸腺肽组CD3+、CD4+、CD4+/CD8+水平较常规组明显改善(P<0.05),CRP和PCT水平较常规组明显下降(P<0.05),临床有效率较常规组明显提高(P<0.05)。结论胸腺肽α1能改善老年COPD患者的免疫功能,联合胸腺肽α1治疗老年COPD急性发作期效果明显。     

Production of human B and T cell growth factors is enhanced by thymic hormones

The thymic preparations thymosin fraction 5 (TF5) and synthetic thymosin alpha 1 (T alpha 1) were examined for their ability to enhance growth factor production by human peripheral blood mononuclear cells (PBMC). The results showed that both TF5 and T alpha 1 were capable of enhancing the production of a B cell growth factor (BCGF-12kD) and T cell growth factor (TCGF; IL-2). Enhancement by T alpha 1 could be obtained at 100-200-fold lower concentrations than that seen with TF5. In contrast, no enhancement of growth factor production was obtained with control preparations of non-thymic tissue extracts at any concentrations used. It was observed that stimulation of BCGF-12kD and IL-2 was most significantly obtained when the PBMC were activated with lectin. Furthermore, no direct effect of thymic hormones on test B and T cells was observed. These observations provide the first direct evidence that production of B cell growth factors can be enhanced by thymic hormones. In addition, these studies suggest that thymic hormones may regulate B cell responses by acting on mature activated T lymphocytes.     

A pilot study of perilymphatic leukocyte cytokine mixture (IRX-2) as neoadjuvant treatment for early stage cervical carcinoma

Clinical and experimental data demonstrate that local cytokines are able to induce tumor regression and in some cases antitumor systemic immune response. IRX-2 is a cell-free mixture of cytokines obtained from unrelated donor lymphocytes with demonstrated ability to induce immune mediated regression of squamous cell carcinomas of head and neck. The objective of this study was to evaluate the antitumor activity and toxicity of IRX-2 in untreated early stage cervical cancer patients. Ten consecutive patients clinically staged IB1, IB2 and IIA were treated with a neoadjuvant immunotherapy regimen that consisted in a single IV dose of cyclophosphamide at 300 mg/m2 on day 1, oral indomethacin or ibuprofen and zinc sulfate were administered from days I to 21 and 10 regional perilymphatic injections of IRX-2 on days 3 to 14. All patients were scheduled for radical hysterectomy on day 21. The clinical and pathological responses, toxicity and survival were evaluated. Clinical response was seen in 50% of patients (three partial responses, two minor responses). Seven patients underwent surgery and pathological tumor reduction associated with tumor fragmentation was found in five cases. Histological studies demonstrated a rather heterogeneous cell type infiltrating pattern in the tumor which included lymphocytes, plasma cells, neutrophils, macrophages and eosinophils. Immunohistochemical analysis of the surgical specimens demonstrated an increase of tumor infiltrating CD8+ cells. The treatment was well tolerated except for mild pain and minor bleeding during injections and gastric intolerance to indomethacin. At 31 months of maximum follow-up (median 29), eight patients are disease-free. Our results suggest that the immunotherapy approach used induces tumor responses in cervical cancer patients. Further studies are needed to confirm these results as well as to elucidate the mechanisms underlying these effects.     

Thymosins alpha 1 and beta 4 potentiate the antigen-presenting capacity of macrophages

The immunomodulatory effects of thymosins on the Ag-presenting capacity of macrophages were investigated. Using an in vitro antigen (Ag)-specific macrophage-dependent T-cell proliferation system, we found that both thymosin alpha 1 (T alpha 1) and thymosin beta 4 (T beta 4) augment the Ag-presenting capacity of macrophages. Macrophage monolayers were pulsed with keyhole limpet hemocyanin (KLH) in the absence or presence of thymosins, washed and overlaid with spleen cells. Splenocytes were collected, mitomycin C-treated and injected into syngeneic mice. Draining lymph node cells were tested for Ag-specific response by measuring proliferation, interleukin 2 (IL-2) secretion and expression of IL-2 receptors (IL-2R) on their cell surface. We found that the presence of thymosins during the pulsing of macrophages with KLH led to significantly enhanced lymph node cell proliferation responses to KLH was correlated to increased IL-2 production and IL-2R expression. The concentrations of T alpha 1 and T beta 4 required for amplification were 10(-8) to 10(-10) M, well within the physiological range of activity of most peptide hormones. The observed enhancement of IL-2 secretion was not accompanied by interleukin 4 (IL-4) production. This study is the first to demonstrate that thymic hormones have the ability to increase the efficiency of antigen presentation by macrophages. The results suggest that an initial step in the regulation of the immune function by T alpha 1 and T beta 4 may involve activation of the macrophages at the time of antigen presentation.     

Thymic hormones.

The thymus produces several polypeptides, which induce lymphocyte differentiation in vitro and in vivo. Several of these polypeptides have been chemically characterized, and three of them have been sequenced and synthesised (alpha 1 thymosin, thymopoietin and the serum thymic factor). Thymic hormones do not act identically on all T-cell subsets: they alter preferentially post-thymic precursor cells, and among mature T cells cytotoxic cells and suppressor cells. Their mode of action at the cellular level involves binding to specific cellular receptors and interaction with adenyl cyclase. Preliminary clinical trials with crude extracts have provided promising results in immunodeficient and cancer patients. The differentiation of T cells from stem cells has been the matter of considerable investigation over the last two decades, since it has been realized that the thymus and its products, the thymus-derived cells (T cells) play a central role in the generation of effector cells in cell-mediated immunity and in the regulation of the various categories of immune responses. That the thymus could act by the intermediate of humoral substances was precociously suggested by MILLER and OSOBA before the observation that thymuses grafted within a cell-impermeable Millipore diffusion chamber restored the immunocompetence of neonatally thymectomized (Tx) mice (1). However, although this experiment was ultimately confirmed by using chambers with well-controlled impermeability (2), MILLER did not pursue the idea of the humoral function of the thymus. Probably, the striking results obtained by DAVIES (3) and other workers, indicating direct migration of functional T cells from the thymus and the poor results initially obtained in trying to reconstitute the immune system of neonatally Tx mice by cell-free thymic extracts contributed to this disappointment. A new impetus was given to the subject in the early 70's when in vitro tests of lymphocyte function became available and when purified extracts of the thymus proved capable of restoring antigen-specific and non-specific immunocompetence of Tx mice. More recently, completely defined synthetic thymic hormones have been obtained. The question is no longer to decide whether thymic hormones exist, but rather to elucidate their biological significance and potential clinical applications. The multiplicity of available factors has created some confusion. It will be the aim of these few pages to review critically the various factors reported in the literature, giving particular emphasis to their pharmacology and their potential use in the modulation of immune responses.     

Thymosin alpha1 accelerates restoration of T cell-mediated neutralizing antibody response in immunocompromised hosts

Thymosin alpha1 is a biological response modifier that has been used clinically for the treatment of chronic hepatitis B viral infection. Both immunomodulatory and immediate intracellular mechanisms have been postulated to explain the effect of thymosin alpha1 on hepatocytes infected with hepatitis B virus (HBV). Here, we established a new animal model and the related suitable conditions to access the thymosin activity by means of measuring the production of neutralizing antibody against hepatitis B surface antigen (HBsAg). We proved that chemically synthesized thymosin alpha1 restored the T cell-mediated antibody production following its suppression in mice by 5-fluorouracil (5-FU), and found that thymosin alpha1 showed activity at a low dose of 30 microg/kg. Further studies utilizing the flowcytometric analysis showed that thymosin alpha1 at this dose accelerated the replenishment and maturation of thymocytes while the expression of Smoothened (Smo) of the Hedgehog (Hh)-signaling in CD4-CD8- thymocytes, the potent negative regulator of proliferative responses, was not affected. The restoration of some of the defects in the host defense systems may facilitate elimination of infectious agents, and the present study provides a novel model to define the restoration of T cell-mediated immune responses to hepatitis B virus in vivo.     

Aspirin and thymosin increase interleukin-2 and interferon-gamma production by human peripheral blood lymphocytes

Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) have recently been added to the arsenal of synthetic biological response modifiers with important immunomodulatory activities. In this paper we have assessed the effects of acetylsalicylic acid (aspirin), thymosin alpha and thymosin fraction 5 (TF5), a partially purified calf thymic preparation, on production of IFN-gamma in vitro. Stimulation by oral aspirin of IL-2 and IFN-gamma production by peripheral blood lymphocytes (PBLs) was also studied in healthy human volunteers. Aspirin, thymosin alpha 1 and TF5 were all observed to enhance phytohemagglutinin (PHA)-stimulated production of IFN-gamma. Peak IFN-gamma production by PHA-stimulated PBLs was observed after 24 h of incubation with TF5 and after 72 h with aspirin. Stimulation by aspirin and TF5 required the presence of macrophages, and was additive and dose-dependent. The additive effects of aspirin and TF5 suggest that these agents act by different mechanisms. Oral administration of aspirin in normal volunteers significantly enhanced production of both IFN-gamma and IL-2. PHA-stimulated IFN-gamma production was greatest 24 h after aspirin ingestion; in contrast, IL-2 production was optimal 10 h after aspirin ingestion. These observations suggest that oral aspirin is an effective biological response modifier in humans and raise the possibility of a novel combination approach to immunomodulation involving cyclooxygenase inhibitors and thymosins.     

Lymph node histology in head and neck cancer: impact of immunotherapy with IRX-2

OBJECTIVE: To determine if lymph nodes (LN) of patients receiving IRX-2 immunotherapy reflect changes in histology. SETTING: National Cancer Institute, Mexico City, Mexico. PATIENTS: Thirty patients with advanced squamous cell carcinoma of the head and neck (H and N SCC) and 10 non-cancer controls. INTERVENTION: A 21-day cycle of preoperative immunotherapy, including a single intravenous infusion of low-dose cyclophosphamide (300 mg/M(2)), 10 or 20 daily perilymphatic injections of a natural cytokine mixture (IRX-2) (approximately 200 U interleukin-2 equivalence by enzyme-linked immunosorbent assay), daily oral indomethacin, and daily oral zinc with multivitamins, followed by surgery (20 patients); surgery only (10 patients); LN biopsy controls (10). OUTCOME MEASURES: Pretreatment biopsies were performed to confirm the diagnosis. Clinical responses were assessed at surgery, and the specimen and a sample of lymph node were analyzed with respect to changes in morphology and lymphoid and inflammatory infiltration (T and B lymphocytes, plasma cells, macrophages, granulocytes, and giant cells). The postsurgical characteristics were ascribed percentages based on a representative section and compared. RESULTS: All 20 H and N SCC patients treated with IRX-2 showed the changes of immune regression of their tumors, previously characterized [Arch. Pathol. Lab. Med. 122 (1998) 447]. The 10 H and N SCC controls showed no such changes. Lymph node histology of the 10 H and N SCC controls showed, compared to non-cancer controls, reduced size, decreased T cell area and density and increased sinus histiocytosis. The lymph nodes of IRX-2-treated H and N SCC patients showed increased size (over both control groups), increased T cell area and density and decreased follicles and sinus histiocytosis. The T cell and/or B cell areas of LN of IRX-2-treated patients showed a high correlation with T and/or B cell infiltration into these tumors (p<0.001). CONCLUSION: The lymph nodes of patients with H and N SCC are distinguished by T cell depletion and sinus histiocytosis (SH). Immunotherapy reverses these changes and induces nodal expansion and lymphoid infiltration into the tumor that correlates with LN changes. The correlation of nodal expansion with tumor lymphoid infiltration and regression implies an effective immunization to host tumor antigens occurring at the level of the regional lymph node. The reversal of sinus histiocytosis, by IRX-2 treatment, in association with nodal expansion suggests that tumor antigen processing via dendritic cells is defective in cancer-bearing patients and that it is corrected by the treatment.     

胸腺肽α_1在结直肠癌术后辅助化疗中的临床应用

目的:观察结直肠癌辅助化疗联合胸腺肽α1对患者免疫功能及骨髓抑制的影响。方法:76例结直肠癌患者随机分为2组,对照组38例,采用单纯FOLFOX4方案化疗;试验组38例,采用FOLFOX4方案化疗联合胸腺肽α1治疗。14d为1周期,连续治疗2个周期后观察化疗前、后外周血T淋巴细胞亚群的变化及血液学毒副反应。结果:化疗后试验组CD4、CD4/CD8、自然杀伤细胞较对照组明显升高(P<0.05);化疗后试验组白细胞计数高于对照组(P<0.05)。结论:结直肠癌辅助化疗联合胸腺肽α1可提高患者的细胞免疫功能,减轻化疗的骨髓抑制。     

儿童慢性乙型肝炎细胞免疫功能及胸腺素疗效

目的　探讨慢性乙型肝炎(CHB)患儿细胞免疫功能及胸腺素疗效。方法　6 0例CHB患儿随机分为常规组(予常规治疗)和胸腺素组(在常规治疗基础上+胸腺素) ,并以6 0例健康儿童作为正常对照组。于治疗前、疗程结束后1mo检测T细胞亚群(CD+ 3 、CD+ 4 、CD+ 8)、血清白细胞介素2 (IL 2 )及可溶性白细胞介素2受体(sIL 2R)水平;定期复查肝功能、乙肝标志物和HBV DNA。结果　与正常对照组比较,CHB组CD+ 3 与CD+ 4 的百分率、CD+ 4 /CD+ 8及血清IL 2水平明显降低(P均<0 0 1) ,CD+ 8百分率及血清sIL 2R水平明显升高(P均<0 0 1) ;与常规组比较,胸腺素组血清ALT明显下降(P <0 0 1) ,ALT复常时间明显缩短(P <0 0 1) ,HBeAg转阴率明显上升(P <0 0 5 ) ,各免疫学指标明显恢复,差异均有统计学意义(P <0 0 1或P <0 0 5 )。结论　CHB患儿细胞免疫功能低下,胸腺素能增强细胞免疫功能,有利于病毒清除和肝功能的恢复     

Restoration of the thymic cellular microenvironment following autologous bone marrow transplantation

Mammalian thymic histogenesis can be morphologically divided into three consecutive stages: 1) epithelial; 2) lymphopoietic or lympho-epithelial; and 3) differentiated cellular microenvironmental, with formation of Hassall's bodies (HBs). The marked reduction of the thymic cellular microenvironment (TCM) is a well-controlled physiological process and is presumably under both local and global regulation by the cells of the RE meshwork and by the neuroendocrine axis, respectively. In humans, the age-related decline of facteur thymique sérique (FTS) levels in blood begins after 20 years of age and FTS completely disappears between the 5th and 6th decade of life. In contrast, serum levels of thymosin-alpha 1 and thymopoietin seem to decline earlier, starting as early as 10 years of age. The influences of other hormones on the thymic involution have also been characterized: testosterone, estrogen and hydrocortisone treatment results in marked involution, cortisone and progesterone administration causes slight to moderate, while use of desoxycorticosterone has no effect. Since the thymus is the primary T-lymphopoietic organ during mammalian ontogenesis, its age-related involution with the typical immunomorphological alterations can be held responsible only for a decline in antigen-specific T-lymphocyte immune functions. Thymic involution and diminished T-lymphocyte proliferation can be partially restored by thymic tissue transplantation or administration of thymic hormones. The stimulus for thymic cell proliferation and differentiation is genetically determined within the organ implant. The only partial reconstitution of CD4+ T-helper-lymphocyte subset after anti-neoplastic chemotherapy and autologous BTM represents a significant, therapy-complicating, clinical problem. After high-dose chemotherapy, the restoration of thymus-dependent CD4+ T-lymphocyte genesis was reported only in children. Our radiation, stem cell transplantation, and hormone treatment experiments in animals resulted in age- and time-dependent regeneration of the cytoarchitecture of the TCM, as well as intrathymic lymphopoiesis.     

Reconstitution of T cell functions in aging mice by thymosin alpha 1

Helper T cell activity of spleen cells from BDF1 mice is impaired by aging but is restored to a large extent by injection of thymosin alpha 1, a synthetic peptide consisting of 28 amino acid residues. Injection of an equimolar amount of the N14 (N-terminal half of thymosin alpha 1) synthetic fragment is at least as effective as the entire alpha 1 molecule in increasing helper T cell activity of spleen cells from old (6-18 months) mice but not from young (3 months) mice. Conversely, injection of the C14 (C-terminal half of thymosin alpha 1) synthetic fragment is devoid of any effect in both young and old mice. Since helper T cell activity of spleen cells from old mice is also increased by injection of interleukin-2, the observed enhancement of interleukin-2 production by mitogen-activated spleen cells from old mice upon injection of thymosin alpha 1 or the N14 fragment suggests that these peptides amplify helper T cell activity by increasing the cell precursor frequency of interleukin-2-producing T cells. This conclusion is further supported by the finding that injection of thymosin alpha 1, or its N14, but not C14, fragment enhances the expression of interleukin-2 receptors on mitogen-activated spleen cells from old but not from young mice.     

Indications for immunotherapy

Underlying immunodeficiency should be suspected in every patient, irrespective of age, who has recurrent, persistent, severe, or unusual infections. Defects in immunity can be classified into primary or secondary disorders involving specific or nonspecific immune mechanisms. Several forms of primary and secondary immunodeficiency exist for which various immunotherapeutic modalities are available. Significant among these are immunoglobulins commercially available for intravenous infusion. Other therapies include transplantation of tissue such as bone marrow, fetal liver, and fetal thymus. Enzyme replacement therapy is being developed, as is the use of products unique to immunocompetent cells, such as thymus extract, thymosin, interleukins, and transfer factor. Forms of nonspecific immune modulators and stimulators are other possibilities, especially in the context of the immunotherapy of tumors.     

Complexes of an Alpha Thymosin Derivative with (185/187) Re and (99m) Tc: Structural Analysis and Initial Biological Evaluation

Alpha thymosins are a family of immunostimulating peptides first isolated from thymus gland. In the present work, the structure of the ReO(V)(3+) complex of an alpha 1 thymosin derivative containing the metal-chelating N,N-dimethylglycyl-l-seryl-l-cysteinyl group was studied with NMR, CD, and ESI. The analysis indicated the existence of two interconverting diastereomers depending on the orientation of the side chain of the chelated Ser syn- or anti- to the oxygen of the ReO(V)(3+) core. The two diastereomers could be separated on HPLC under a slow gradient showing the ratio of syn/anti to be 3:2, in agreement with the NMR data. The conversion process was shown to involve the coordination of a water molecule to the ReO(V)(3+) core through the incubation of the complex in (18) O-enriched water and subsequent ESI analysis. HPLC analysis of the analogous radioactive (99m) TcO(V)(3+) complex showed the formation of two isomers in the same syn/anti 3:2 ratio. Biodistribution studies of the (99m) TcO(V)(3+) complex in Swiss albino mice with experimentally induced inflammation showed higher accumulated radioactivity in inflamed tissue compared to normal (ratio of inflamed/control tissue 3.9). (99m) Tc-labeled complexes of alpha thymosin derivatives are expected to facilitate research on alpha thymosins and accelerate exploitation of these peptides in immunotherapy protocols.     

Current concepts in clinical therapeutics: immunologic treatment of human immunodeficiency virus infections

An overview of the immune system is presented, and the pathogenesis, transmission, diagnostic tests, diagnosis, immunotherapy, and vaccine development for human immunodeficiency virus (HIV) are reviewed. More than 42,000 cases of acquired immunodeficiency syndrome (AIDS) have now been reported in the United States, and an additional 250,000 cases are expected by 1991. The immunopathogenesis of HIV infection involves both cellular and humoral components of the immune system, with a characteristic depletion of helper T lymphocytes, impaired delayed hypersensitivity, and polyclonal B-cell activation. Monocytes and macrophages are also infected, and these cells provide a transport mechanism into the central nervous system. HIV is transmitted primarily by sexual, blood, and perinatal mechanisms. Enzyme-linked immunosorbent and Western blot assays are used in diagnostic tests, and diagnosis of AIDS is based on the presence of secondary infection or tumor at least moderately indicative of cellular immune deficiency in the absence of predisposing factors. Three approaches are being tested for treating HIV infection: immunomodulators, vaccines, and antiviral agents. Immunomodulators--including interferons, interleukin-2, immune reconstitution with bone-marrow transplantation and lymphocyte transfusions, transfer factor, granulocyte-macrophage colony-stimulating factor, inosine pranobex (isoprinosine), and naltrexone--are being tested with no great successes. Various approaches to vaccine development, including genetically engineered subunit proteins, synthetic peptides, and infectious recombinant viruses, are being considered. Primary immune responses do result from at least one vaccine. Future studies will evaluate combination approaches to therapy. HIV infections confront the health-care system with a serious challenge. It is too early to assess the effectiveness of the various therapeutic strategies for immune deficiencies caused by HIV.     

胸腺素口服对小鼠免疫功能的影响

观察了小牛和猪胸腺素口服1.25、2.5和5.0mg/kg剂量对~(60)Co照射致免疫功能低下小鼠的影响,结果表明口服胸腺素可以提高小鼠的免疫功能,未见种属差异和量效关系。提示胸腺素口服具有临床使用价值。     

The therapeutic potential of 4-1BB (CD137) in cancer

Techniques for modulating immune cells for cancer therapy have been widely studied. One key approach that is being clinically tested is developing tumor-destructive cell-mediated immune responses by regulating co-stimulatory molecules. 4-1BB (CD137), a member of the TNF receptor family, is expressed following activation of T and NK cells. Recently, it has been reported that DCs also express 4-1BB. Cross-linking of 4-1BB provides a potent co-stimulatory signal for lymphocytes via signal transduction pathways that modulate a number of cellular responses. One remarkable response is stimulation of anti-tumor activity in vivo and in vitro. We here review the potential role of 4-1BB in cancer immunotherapy focusing on the cellular and molecular mechanisms involved.     

胸腺肽α1对老年重症医院获得性肺炎患者免疫功能的影响

目的:探讨胸腺肽α1治疗对老年重症医院获得性肺炎(SHAP)患者细胞免疫功能的影响及其临床意义。方法:48例SHAP患者随机分为治疗组和对照组。治疗组在对照组基础上给予胸腺肽α1 1.6 mg皮下注射,qd,持续1周,之后改为1.6 mg,皮下注射,隔日一次,共2周。结果:治疗组治疗后单核细胞人类白细胞抗原(HLA-DR)、自然杀伤(NK)细胞、CD4+细胞及CD4+/CD8+比值明显上升;治疗组住院死亡率明显低于对照组,其存活者抗生素应用时间亦比对照组明显缩短。结论:胸腺肽α1能提高SHAP患者免疫功能,有利于感染控制,并降低住院死亡率。