Upregulated interleukins (IL-6, IL-10, and IL-13) in immunoglobulin G4-related aortic aneurysm patients

Objective

Immunoglobulin (Ig) G4-related aortic aneurysms (IgG4-AAs) are a special aortic aneurysm among IgG4-related diseases (IgG4-RDs), which are inflammatory and fibrous conditions characterized by tumorous swelling of affected organs and high serum IgG4 concentrations. Recently, IgG4-RD pathogenesis was shown to be associated with T-helper-2 (Th2) and regulatory T (Treg) dominant cytokine production, such as interleukin (IL)-4, IL-10, and IL-13. IL-6 is a key proinflammatory cytokine contributing to lymphocyte and plasmacyte maturation and to atherosclerosis and aneurysm development. We serologically and histopathologically evaluated the cytokine profile in IgG4-AA patients.

IL-1 beta induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells.

Overuse injuries and trauma in tendon often involve acute or chronic pain and eventual matrix destruction. Anti-inflammatory drugs have been used as a treatment, however, the cellular and molecular mechanisms of the destructive processes in tendon are not clearly understood. It is thought that an inflammatory event may be involved as an initiating factor. Mediators of the inflammatory response include cytokines released from macrophages and monocytes. Interleukin-1 beta (IL-1 beta) is a candidate proinflammatory cytokine that is active in connective tissues such as bone and cartilage. We hypothesized that tendon cells would express receptors and respond to IL-1 beta in an initial "molecular inflammation" cascade, that is, connective tissue cell expression of cytokines that induce matrix destructive enzymes. This cascade results in expression of matrix metalloproteinases (MMPs) and aggrecanases that may lead to matrix destruction. Normal human tendon cells from six patients were isolated, grown to quiescence and treated with human recombinant IL-1 beta in serum-free medium for 16 h. Total RNA was isolated and mRNA expression assessed by semiquantitative RT-PCR. IL-1 beta (1 nM) induced mRNAs for cyclooxygenase 2 (COX2), MMP-1, -3, -13 and aggrecanase-1 as well as IL-1 beta and IL-6, whereas mRNAs for COX1 and MMP-2 were expressed constitutively. The IL-1 beta-treated tendon cells released prostaglandin E(2) (PGE(2)) in the medium, suggesting that the inducible COX2 catalyzed this synthesis. Induction of PGE(2) was detectable at 10 pM IL-1 beta. IL-1 beta also stimulated MMP-1 and -3 protein secretion. Induction of MMP-1 and -3 was detectable at 10 pM IL-1 beta. Post-injury or after some other inciting events, exogenous IL-1 beta released upon bleeding or as leakage of local capillaries may drive a proinflammatory response at the connective tissue cell level. The resulting induction of COX2, MMP-1 and -3 may underscore a potential for nonlymphocyte-mediated cytokine production of MMPs that causes matrix destruction and a loss of tendon biomechanical properties. Endogenous IL-1 beta might contribute to the process through a positive feedback loop by stimulating expression and accumulation of MMPs in the tendon matrix.     

Influence of pathogens and moderate leukocytes on seminal interleukin (IL)-6, IL-8, and sperm parameters

Purpose

To evaluate the role of pathogens and moderate leukocytes on seminal interleukin (IL)-6, IL-8, and sperm parameters in men undergoing infertility investigation.

Methods

Semen samples from men (n = 171) were divided into three groups on the basis of leukocyte count: no leukocytes (L?; ≤0.1 × 10⁶/ml Mio/ml), moderate leukocytes (L±; >0.1 × 10⁶/ml and <1 × 10⁶/ml), and high leukocytes (=leukocytospermia) (L+; ≥1 × 10⁶/ml). Each group was further classified into two subgroups, according to the presence (B+) or absence (B?) of pathogens. IL-6, IL-8, and sperm characteristics were analyzed in each subgroup. A correlation test was performed to show the association between inflammatory parameters and sperm characteristics.

Results

No significant differences in leukocyte count, cytokine levels, and sperm characteristics were apparent in subgroups with and without pathogens. Grade b motility was significantly lower in subgroup IIa (L±,B?) than in subgroup Ia (L?,B?)(p < 0.05). More significant limitations in sperm motility (lower rapid progressive motility and increased percentage of immotile sperm) were observed in subgroup IIIa (L+,B?) compared with subgroup Ia (p < 0.05). Moderate and high leukocytes increased significantly cytokine levels (p < 0.001).

Conclusions

Moderate leukocyte counts could be an indicator of male genital tract inflammation. Seminal pathogens have no influence on cytokine levels and sperm parameters.     

Expression of Interleukin-6 (IL-6) and IL-6 receptor mRNA in human bone samples from pre- and postmenopausal women.

Interleukin-6 (IL-6) has been attributed to induction of osteoclastogenic-precursor cell proliferation and maturation. Estrogens suppress IL-6 production in stromal/osteoblastic cells in vitro. Conversely, estrogen withdrawal is associated with increased IL-6 production. IL-6 is therefore thought to be an important mediator of the increased bone resorption after menopause. However, evidence supporting a rise in the expression of IL-6 or the IL-6 receptor in human bone tissue with menopause is still lacking. To address this question, we established a 5'-nuclease assay to quantitate the expression of human IL-6 and the gp80 subunit of the IL-6 receptor in human bone samples. The number of mRNA copies was normalized to the number of copies of beta actin mRNA. Osteocalcin expression served as an independent control. The study population consisted of 169 women (mean age 52.4 +/- 11.6 years) who underwent surgery for early breast cancer. Serum IL-6 was measured by enzyme-linked immunosorbent assay, serum crosslaps as a marker of bone resorption were measured by electrochemiluminescent assay, and serum osteocalcin was measured by chemoluminescence assays. RNA expression of osteocalcin in bone tissue from early postmenopausal women was higher compared with premenopausal women. Local expression was positively associated with circulating osteocalcin and crosslaps concentrations. Postmenopausal women also had higher circulating IL-6 concentrations. In contrast, bone samples from postmenopausal women lacked an increased expression of either IL-6 or gp80 compared with bone samples from premenopausal women. In conclusion, we failed to detect local increases in IL-6 or IL-6 receptor expression in human bone tissue with menopause. If direct changes in the IL-6 system in bone tissue are involved in postmenopausal bone loss, these changes appear to be below the detection limit of our assay system.     

TNF-alpha, IL-6, IFN-gamma, and IL-10 gene expression polymorphisms and the IL-4 receptor alpha-chain variant Q576R: effects on renal allograft outcome.

BACKGROUND: There has been much interest recently in the effects of various cytokine gene expression polymorphisms on graft outcome. However, the results of these investigations reveal the outcomes to be organ-specific and center-specific. We sought to confirm and add to some of the earlier findings by studying the impact of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6) polymorphisms and the interleukin-4 (IL-4) receptor alpha-chain variant on posttransplant renal allograft outcome. METHOD: TNF-alpha, IL-6, IFN-gamma, and IL-10 gene promoter region polymorphisms were assayed genotypically by PCR-SSP on 120 patients transplanted at the Albany Medical Center. These patients were also typed for the IL-4 receptor alpha-chain variant Q576R. RESULTS: Producers of high levels of the proinflammatory cytokine TNF-alpha were found to be at increased risk for acute rejection episodes if the allograft was mismatched for the molecular products of the class II region of the human major histocompatibility complex (HLA-DR). Expression level polymorphisms of the IL-6, IFN-gamma, and IL-10 genes were not associated with acute rejection episodes, nor was the IL-4 receptor alpha-chain variant Q576R. CONCLUSIONS: These data would suggest that the production of high levels of the cytokine TNF-alpha is especially detrimental to graft survival when the recipient's T-helper lymphocytes are being activated by mismatched donor HLA-class II antigens. Typing all potential kidney recipients for TNF-alpha, and providing well-matched organs for high producers of this cytokines, may be expected to increase rejection-free graft survival in these patients.     

Influence of pro-inflammatory (IL-1 alpha,IL-6, TNF-alpha,IFN-gamma) and anti-inflammatory (IL-4) cytokines on chondrocyte function

OBJECTIVE: Cytokines produced by inflammatory cells play a pivotal role in synovial inflammation and joint destruction in rheumatoid arthritis. To investigate the influence of pro-inflammatory cytokines (IL-1 alpha, IL-6, TNF-alpha, IFN-gamma) and subsequently the possible beneficial role of an anti-inflammatory cytokine (IL-4) on chondrocyte viability (necrosis/apoptosis), proliferation and nitric oxide (NO) production. METHODS: Primary bovine chondrocytes were cultured until monolayers were obtained. Cells were incubated with cytokines (IL-1 alpha, IFN-gamma, TNF-alpha, IL-4, IL-6) at 0.1, 1, 10 and 100 ng/mL. After 48 h, the viability of the chondrocytes was measured flow cytometrically with propidium iodide. Proliferation was determined by the incorporation of tritiated thymidine. The morphology of the chondrocytes, including presence of apoptotic nuclei, was evaluated by a May-Grünwald-Giemsa staining. In addition, the number of apoptotic chondrocytes was detected flow cytometrically with a TUNEL technique and annexin-V/propidium iodide staining. NO production was evaluated using a spectrophotometric assay, based upon the Griess reaction. RESULTS: The viability and proliferation of bovine chondrocytes decreased after incubation with 100 ng/mL IL-1 alpha, TNF-alpha or IFN-gamma. In contrast, incubation of chondrocytes with IL-4 or IL-6 had no influence on the viability or the proliferation of cells. IL-1 alpha was able to enhance NO production in a dose dependent manner. IFN-gamma and TNF-alpha induced NO production only at the highest concentration (100 ng/mL), whereas IL-4 and IL-6 did not. There was a dose dependent increase in apoptosis of bovine chondrocytes cultured in the presence of IL-1 alpha and TNF-alpha. This effect could not be prevented by preincubation with IL-4. Preincubation with IL-4 diminished IL-1 alpha and TNF-alpha induced NO production and increased proliferation of chondrocytes. In an additional experiment, incubation of human chondrocytes with anti-Fas did not induce apoptosis as measured by annexin-V/propidium iodide staining. CONCLUSIONS: Pro-inflammatory cytokines are able to induce apoptosis, whereas IL-4 as an anti-inflammatory cytokine can inhibit the effect of IL-1 alpha and TNF-alpha on NO production and proliferation of bovine chondrocytes.     

Doxazosin and serotonin (5-HT) receptor (1A, 2A, and 4) antagonists inhibit 5-HT-mediated human cavernosal contraction

Penile erection results from the balance between relaxation and contractile mechanisms of the corpus cavernosum. Only a few studies suggest a role for endogenous contractile agents such as 5-hydroxytryptamine (5-HT). Our aim was to confirm the possible role of 5-HT in human erection. The effect of 5-HT on human cavernosal tissues, as well as those of doxazosin (shown previously to have 5-HT inhibitory action), ketanserin (5-HT (2A) receptor antagonist), NAN-190 (5-HT (1A) receptor antagonist), and SB 203186 (5-HT (4) receptor antagonist) on 5-HT-mediated effects, were assessed using the organ bath technique, including electrical field stimulation study (EFS). Results are presented as median (mg/mg = mg contraction/mg of tissue). Consistent 5-HT-mediated (10(-3) M) contractions were demonstrated (n = 18; 63 mg/mg). These contractions were inhibited with ketanserin by 90% (n = 8), NAN-190 by 68% (n = 12), and SB 203186 by 55% (n = 12). Doxazosin showed a similar 5-HT inhibitory action in a concentration-dependent manner (10(-4) M; 94% reduction; n = 8, 10(-6) M; 68.3% reduction; n = 8). Our EFS studies indicated the presence of neuronally derived 5-HT and that a majority of the nonnoradrenogenic contraction (54%) was mediated via 5-HT(2A) receptors. These findings suggest that 5-HT may play a role in the human detumescence process via 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors. Neuronally released 5-HT is probably an important contractile neurotransmitter in the erectile process. Doxazosin, ketanserin, and 5-HT(1A) and 5-HT(4) receptor antagonists may be useful as part of combination therapy used to treat erectile dysfunction.     

肝癌、胃癌、大肠癌外周血T淋巴细胞丝裂原反应性和血浆IL-2、IL-6活性及IL-2受体的表达

目的 探讨肝癌、胃癌、大肠癌发病机理。方法 应用生物测定法检测肝癌、胃癌、大肠癌外周血T淋巴细胞丝裂原反应性和血浆白细胞介素-2(IL-2)、白细胞介素-6(IL-6)活性及可溶性白细胞介素-2受体(IL-2R)的表达。结果 肝癌、胃癌、大肠癌患者T淋巴细胞丝裂原反应性和血浆IL-2、IL-6活性均显著低于对照组．而IL-2R表达却均显著高于对照组。结论 肝癌、胃癌、大肠癌患者外周血T淋巴细胞功能被严重抑制．IL-2、IL-6和IL-2R可能在该病的发病机制中起一定作用。     

选择性脾胃区减断分流术对血清IL-4,IL-6和sIL-2R水平的影响

目的探讨门静脉高压症脾功能亢进患者行选择性脾胃区减断分流术(selective decongestive devascularization shunt of gastrosplenic region,SDDS-GSR)后血清白介素-4(Interleukin-4,IL-4)、白介素-6(Interleukin-6,IL-6)和游离白介素-2受体(soluble interleukin-2 receptor,sIL-2R)水平的变化及意义。方法ELISA法检测8例SDDS-GSR术后1～3年门脉高压症患者血清IL-4,IL-6和sIL-2R水平,并与正常人及门脉高压症非手术患者作对照研究。结果门脉高压症非手术患者血清IL-4,IL-6和sIL-2R水平分别为(15.67±3.15)pg/ml,(3.16±1.30)pg/ml和(161.03±30.61)pg/ml,较正常组显著升高(P<0.01),SDDS-GSR术后IL-6,sIL-2R水平分别为(2.11±0.59)pg/ml和(124.98±36.93)pg/ml,较非手术组降低有统计学意义(P<0.05),但仍显著高于正常组(P<0.05)。结论IL-6和sIL-2R的分泌调节紊乱在肝硬化发病机制中起重要作用,SDDS-GSR术可有效缓解脾亢,显著降低患者血清IL-6和sIL-2R水平,表明有利于肝功能的维护和缓解肝硬化进展。     

Effects of intravenous anesthetics on interleukin (IL)-6 and IL-10 production by lipopolysaccharide-stimulated mononuclear cells from healthy volunteers

BACKGROUND: Surgical trauma has been shown to augment the plasma concentrations of proinflammatory cytokines, which are important mediators of host defense mechanisms and the systemic inflammatory response syndrome (SIRS). Recently, it has been shown that certain kinds of surgery provoke not only a proinflammatory response (SIRS) but also a concurrent anti-inflammatory response. The aim of this study was therefore to examine the effects of intravenous anesthetics on the synthesis of interleukin (IL)-6 (a proinflammatory cytokine) and IL-10 (an anti-inflammatory cytokine) by lipopolysaccharide (LPS)-stimulated mononuclear cells from healthy volunteers. METHODS: Peripheral blood mononuclear cells (PBMCs) from 17 healthy volunteers, separated by centrifugation on a Ficoll-Hypaque gradient, were washed and suspended in RPMI containing 10% heat-inactivated fetal calf serum (FCS). After adding RPMI-FCS containing various concentrations of intravenous anesthetics (propofol, thiopental, ketamine and midazolam), the PBMCs were incubated overnight in the presence of a submaximal concentration of LPS. The supernatants were collected and their IL-6 and IL-10 contents were assayed using enzyme-linked immunosorbent assay kits. RESULTS: Propofol inhibited both IL-6 and IL-10 production at 0.5 microg/mL, 5 microg/mL and 50 microg/mL. Conversely, thiopental induced IL-10 production at 2 microg/mL and 20 microg/mL. CONCLUSION: Propofol appears to inhibit both IL-6 and IL-10 production by LPS-stimulated PBMCs in vitro. Further study is required to clarify the mechanism of the suppressive effect of propofol.     

肿瘤浸润性淋巴细胞在白细胞介素-2、-4协同下局部过继免疫治疗膀胱癌的实验研究

目的　观察膀胱癌肿瘤浸润性淋巴细胞 (TIL)联合不同细胞因子瘤灶内过继免疫抗癌的效应及对机体全身抗肿瘤免疫机制的影响。方法　建立BTT73 9动物模型 ,分离、培养TIL。采用正交设计实验方法 ,将TIL、白细胞介素 (IL) 2、 4及三因素交互组合悬液分别直接注射至瘤体内 ,定期测量肿瘤体积 ,免疫治疗 2周后检测NK细胞活性、T淋巴细胞转刺激指数 ,观察组织学及超微结构变化。结果　比较对照组 ,治疗 2周时各TIL相关组均不同程度抑制了膀胱肿瘤体积的增长 ,且NK细胞活性及T淋巴细胞转化增殖能力得以提高 (P <0 .0 5 )。TIL/IL 2疗法明显抑制了瘤体的增长 ,免疫治疗 1周后即表现出协同增强效应 (P <0 .0 5 ) ,而NK细胞活性及T淋巴细胞转刺激指数也显著提高 (P <0 .0 5 )。TIL/IL 2 /IL 4组获得了较强的抗癌功效 ,但与TIL/IL 2组差异无显著性 (P >0 .0 5 )。超微结构变化显示出TIL强烈的溶癌现象。结论　TIL在细胞因子特别是IL 2协同下瘤灶内注射的局部免疫疗法 ,具有较强的抗膀胱癌效应 ,并显著提高了机体全身抗瘤免疫功能。     

Localization of bone morphogenetic proteins (BMPs)-2, -4, and -6 within megakaryocytes and platelets

In this study, we localized bone morphogenetic proteins (BMPs), proteins known to induce ectopic osteogenesis, within megakaryocytes and in lysates of human platelets. Immunohistochemistry localized BMP-2, -4, and -6 within marrow megakaryocytes of 5-week-old rat tibias. In situ hybridization was utilized to confirm the presence of BMP-2, BMP-4, and BMP-6 mRNA in 2- to 3-week-old mouse tibial marrow megakaryocytes. Finally, the presence of BMP-2, -4, and -6 was confirmed in human platelet lysates using Western blot technique. The expression and release of BMPs by megakaryocytes, within platelets and perhaps by secretion, may help to explain recent reports of excessive bone formation associated with increased numbers of marrow megakaryocytes in GATA-1- or NF-E2 gene-deficient mice. Also, excess local release of BMPs may provide an explanation for the bone overgrowth (osteosclerosis) seen in human patients suffering from a type of myelogenous leukemia characterized by increased numbers of marrow megakaryocytes.     

人甲状旁腺素(1-34)对新生鼠成骨细胞钙含量及钙化结节形成的影响

目的研究外源性ｈＰＴＨ（１－３４）对新生大鼠成骨细胞基质钙含量及钙化结节形成的影响。方法新生大鼠成骨细胞原代培养,原子吸收分光光度法测细胞基质钙含量,ｖｏｎＫｏｓｓａ染色鉴定钙化结节。结果１０－１０～１０－７ｍｏｌ·Ｌ－１ｈＰＴＨ（１－３４）持续作用于细胞,基质钙含量与对照相比显著降低;１０－８ｍｏｌ·Ｌ－１ｈＰＴＨ（１－３４）在以４８小时为一循环的前１２小时给药循环８次时基质钙含量达最高峰,与对照组相比增加５７６％,且形成钙化结节最多。结论ｈＰＴＨ（１－３４）刺激成骨细胞基质钙含量及钙化结节形成与给药方式及药物浓度有关,低浓度间歇性给与ｈＰＴＨ（１－３４）能提高成骨细胞基质钙及促进钙化结节形成。     

The effects of S(-)-, R(+)-, and racemic bupivacaine on lysophosphatidate-induced priming of human neutrophils

Local anesthetics modulate inflammatory responses and may therefore be potentially useful in mitigating perioperative inflammatory injury. The inflammatory modulating effects of S(-)-bupivacaine are not known. Therefore, we compared the effects of S(-)-bupivacaine, R(+)-bupivacaine, and racemic bupivacaine on neutrophil function and receptor signaling. Priming (by lysophosphatidic acid [LPA]) and activation (by N-formylmethionine-leucyl-phenylalanine) of superoxide release by isolated human neutrophils was studied by using a cytochrome c-reduction assay. LPA receptor signaling in Xenopus oocytes was studied by using voltage clamp. All three local anesthetics were without effect on activation. S(-)-Bupivacaine inhibited priming more than did racemic bupivacaine; R(+)-bupivacaine was without effect. At 10(-4) M, S(-)-bupivacaine inhibited approximately 50%. Comparable results were obtained in our recombinant model, where S(-)-bupivacaine most effectively inhibited LPA signaling. Compared with racemic bupivacaine and other anesthetics, S(-)-bupivacaine appears particularly effective in suppressing neutrophil priming, a process responsible in part for the overactive neutrophil response. IMPLICATIONS: Overactive inflammatory responses underlie several perioperative disorders. Compared with racemic bupivacaine and other anesthetics, S(-)-bupivacaine appears particularly effective in suppressing neutrophil priming, a process responsible in part for the overactive neutrophil response.     

Association of circulating interleukin (IL)-12- and IL-10-producing dendritic cells with time posttransplant, dose of immunosuppression, and plasma cytokines in renal-transplant recipients

BACKGROUND: Interleukin (IL)-12-producing dendritic cells (IL-12+DC) polarize T helper (Th) differentiation toward Th1, whereas IL-10+DC induce Th differentiation toward Th2. We investigated DC and plasma cytokine patterns early and late after transplantation. METHODS: Twenty-five hospitalized renal-transplant recipients without acute rejection or infection early (<40 days) posttransplant, 32 symptom-free outpatients with long-term functioning transplants (2,762+/-2,423 days posttransplant), and 17 healthy controls were studied. The intracellular production of IL-12 and IL-10 in CD11c+ CD83+ CD40+ DC was measured in freshly obtained whole blood using four-color fluorescence flow cytometry. In addition, plasma cytokine levels were investigated. RESULTS: Early and late posttransplant patients had significantly lower proportions of IL-12+DC (early: P=0.001; late: P=0.034) and lower ratios of IL-12+/IL-10+DC (early: P=0.0001; late: P<0.0001) than healthy controls. IL-10+DC (P=0.0004) and IL-12+DC (P=0.002) increased with time posttransplant in association with dose reductions of cyclosporine (IL-10+DC: P=0.003; IL-12+DC: P=0.005), methylprednisolone (IL-10+DC: P<0.0001; IL-12+DC: P=0.001) and mycophenolate mofetil (IL-10+DC: P<0.0001; IL-12+DC: P=0.004). Both IL-10+DC and IL-12+DC were associated with low plasma IL-10 (IL-10+DC: P=0.010; IL-12+DC: P=0.011) and high plasma IL-6 (IL-10+DC: P=0.001; IL-12+DC: P=0.009). IL-10+DC were also associated with high plasma levels of IL-3 (P=0.003), interferon (IFN)-gamma (P=0.014), and IL-2 (P=0.058). CONCLUSION: IL-10+DC and IL-12+DC in peripheral blood are associated with time after transplantation and dosage of immunosuppression. IL-10+DC dominate late posttransplant in the presence of Th1 plasma cytokines (high IFN-gamma and IL-2), high IL-3, and low IL-10. These findings could be a reflection of immunoregulatory processes favoring long-term allograft acceptance.     

重组人胰岛素样生长因子I对大鼠成骨细胞增殖、凋亡及I型胶原蛋白合成的影响

目的观察胰岛素样生长因子I(IGF-I)对体外培养的大鼠成骨细胞的增殖、凋亡及I型胶原蛋白合成的影响,探讨IGF-I对骨代谢影响的可能机制。方法不同浓度rhIGF-I刺激体外培养的大鼠成骨细胞,采用噻唑蓝(MTT)法测定细胞增殖能力;肿瘤坏死因子α(TNF-α)单独或与rhIGF-I共同刺激成骨细胞,流式细胞仪检测细胞周期和凋亡率;rhIGF-I刺激成骨细胞,免疫细胞化学结合计算机图像分析系统检测I型胶原蛋白的表达。结果一定浓度IGF-I能明显增加成骨细胞数量(P<0·05),在0·1~100ng/ml这种作用与IGF-I的浓度呈正相关;TNF-α在0·1~100ng/ml浓度范围内呈剂量依赖性地促进成骨细胞凋亡(P<0·05),并使S期细胞减少(P<0·05),而IGF-I能抑制TNF-α对成骨细胞的促凋亡作用(P<0·05);经IGF-I的刺激,成骨细胞I型胶原蛋白的表达明显高于对照组(P<0·05)。结论IGF-I对大鼠成骨细胞有明显的促增殖作用,在0·1~100ng/ml之间呈浓度依赖性,IGF-I能抑制TNF-α诱导的大鼠成骨细胞凋亡,IGF-I能促进大鼠成骨细胞I型胶原蛋白的合成。