PSS病人血清IL—2,IL—4,IL—6水平的测定

本文用生物测定法技术检测了３０例进行性系统性硬化症患者血清中白细胞介素２、白细胞介素４、白细胞介素６的水平，结果表明：在ＰＳＳ患者血清中，ＩＬ－２、ＩＬ－４的检出率显著高于对照组，ＩＬ－６的检出率虽然高于对照组，但是在统计学上无显著差异。结果提示：ＩＬ－２、ＩＬ－４可能在该病的发病机制中起一定作用。     

可溶性IL－2R在选择性IgA缺乏症发病机理中的意义

白细胞介素２（ＩＬ－２）及其受体（ＩＬ－２Ｒ）系统在机体免疫调节中发挥着重要作用。本研究首先以间接免疫荧光技术检测了选择性ＩｇＡ缺乏症（ＳＩｇＡＤ）患儿活化淋巴细胞膜表面白细胞介素２受体（ｍＩＬ－２Ｒα）的表达情况及其Ｔ细胞亚类水平，继而采用双抗体夹心ＥＬＩＳＡ法检测了ＳＩｇＡＤ患儿血清可溶性白细胞介素２受体（ＳＩＬ－２Ｒα）的含量。结果表明：ＳＩｇＡＤ患儿组的Ｔａｃ阳性细胞百分率（ｍＩＬ－２Ｒα）明显高于正常对照组，其ＣＤ４＋细胞百分率明显低于正常对照组、ＣＤ８＋细胞百分率明显高于正常对照组。而其血清ＳＩＬ－２Ｒα含量亦明显高于正常对照组。研究显示：ＳＩｇＡＤ患儿ｍＩＬ－２Ｒα的表达虽高于正常对照组，但因其Ｔ细胞亚类的显著异常既有体内存在着明显的细胞免疫功能的损害，导致ＩＬ－２的生成不足，使高水平的ＳＩＬ－２Ｒα大量脱落成为ＳＩＬ－２Ｒα，而ＳＩＬ－２Ｒα又可与ＳＩＬ－２Ｒα竞争结合ＩＬ－２，从而使机体细胞免疫功能的损害进一步加剧。     

扩张型心肌病IL－6及IL－1活性的初步研究

应用ＭＴＴ比色法及ＣｏｎＡ活化小鼠胸腺细胞增殖法检测了３０例扩张型心肌病（ＤＣＭ）患者及２０例正常人（ＮＣ）的血清白细胞介素６（ＩＬ－６）、白细胞介素１（ＩＬ－１）的活性，结果发现ＤＣＭ患者ＩＬ－６及ＩＬ－１活性均明显高于ＮＣ组（Ｐ＜０．００１，Ｐ＜０．０１）。提示：ＩＬ－６及ＩＬ－１功能紊乱参与了ＤＣＭ的病理过程。     

病毒性肝炎患者IL－1、IL－6和TNFα活性的检测

检测了甲、乙型病毒性肝炎患者外周血单个核细胞（ＰＢＭＣｓ）ＩＬ－１、ＩＬ－６和ＴＮＦα的诱生活性及其血清中活性。结果表明，乙型慢性活动性肝炎（ＣＡＨ）、乙型肝炎后肝硬化（ＨＣ）和乙型重型肝炎（ＳＨ）ＰＢＭＣｓ经脂多糖诱导后，ＩＬ－１活性分别为３５３１．１±８８２．７Ｕ／ｍ１、２７６９．７±７３０．４±Ｕ／ｍｌ和５３２９．３±１０８９．３Ｕ／ｍｌ，高于正常对照组（Ｐ＜０．０５或（０．０１）；ＩＬ－６诱生活性分别为３８．９０±１４．７５Ｕ／ｍ１、２．４５±１８．８５Ｕ／ｍｌ和７１．９５±２８．０５Ｕ／ｍｌ（与正常对照组相比，ｐ＜０．０５或＜０．０１）；ＴＮＦα诱生活性在乙型慢性迁延性肝炎（ＣＰＨ）、ＣＡＨ、ＨＣ和ＳＨ中分别为３３．２３±７．２５Ｕ／ｍｌ、６．９９±１．８４Ｕ／ｍ１、４．２９±２．１７Ｕ／ｍｌ和８６．７０±２４．１８Ｕ／ｍｌ，与对照组相比Ｐ＜０．０５或Ｐ＜０．０１。各型患者血清中ＩＬ－１、ＩＬ－６和ＴＮＦα活性均有不同程度的增高。文中对ＳＨ患者ＩＬ－１、ＩＬ－６和ＴＮＦα之间的相互关系进行了探讨。     

格林—巴利综合征患者血清及脑脊液中白细胞介素6水平测定

应用生物学方法检测了２６例格林－巴利综合征（ＧＢＳ）患者血清及脑脊液中白细胞介素６（ＩＬ－６）含量。结果显示：ＧＢＳ患者血清及脑脊液中ＩＬ－６水平明显高于正常对照组（Ｐ〈０．００１）；血清中ＩＬ－６含量与脑脊液中ＩＬ－６含量无相关性；血清中ＩＬ－６含量与血清免疫球蛋白含量无相关性；但血清免疫球蛋白水平明显高于正常对照组（Ｐ〈０．０１），提示Ｂ淋巴细胞在ＧＢＳ免疫机制中可能处于激活状态。     

宫颈癌细胞产生的免疫抑制因子对IL－2作用的影响

人宫颈癌细胞产生的免疫抑制因子（ＴＤＳＦ）作用于人外周血单个核细胞（ＰＢＭＣ）６ｈ，即可抑制白细胞介素２（ＩＬ－２）产生，与对照组相比，Ｐ＜０．０１。当ＴＤＳＦ存在时，经ＰＨＡ－Ｐ驯化的ＰＢＭＣ效应细胞对外源性ＩＬ－２反应显著减弱，表明ＴＤＳＦ能抑制ＩＬ－２的作用。ＰＨＡ－Ｐ刺激ＰＢＭＣ增殖，但ＴＤＳＦ使其增殖抑制。表明ＴＤＳＦ能抑制ＩＬ－２产生及其作用；抗癌药对ＴＤＳＦ的分泌有部分阻抑作用。     

宫颈癌细胞产生的免疫抑制因子对IL－2作用的影响

人宫颈癌细胞产生的免疫抑制因子（ＴＤＳＦ）作用于人外周血单个核细胞（ＰＢＭＣ）６ｈ，即可抑制白细胞介素２（ＩＬ－２）产生，与对照组相比，Ｐ＜０．０１。当ＴＤＳＦ存在时，经ＰＨＡ－Ｐ驯化的ＰＢＭＣ效应细胞对外源性ＩＬ－２反应显著减弱，表明ＴＤＳＦ能抑制ＩＬ－２的作用。ＰＨＡ－Ｐ刺激ＰＢＭＣ增殖，但ＴＤＳＦ使其增殖抑制。表明ＴＤＳＦ能抑制ＩＬ－２产生及其作用；抗癌药对ＴＤＳＦ的分泌有部分阻抑作用。     

肾病综合征患儿血清IL-6和sIL-2R测定

检测了３５例肾病综合征（ＮＳ）患儿血清白细胞介素 ６（ＩＬ ６），血清可溶性白细胞介素 ２受体（ｓＩＬ ２Ｒ）含量的变化。结果表明，患儿血清中ＩＬ ６、ｓＩＬ ２Ｒ较对照组显著增高（Ｐ值均＜００１），提示患者体内细胞免疫与体液免疫应答过程参与了ＮＳ...     

慢性肝病、肝癌患者IL－1、IL－8及TNFα活性测定

对２８例慢性肝炎、２３例肝炎性肝硬化及２６例原发性肝癌患者血清中ＩＬ－１、ＩＬ－８及ＴＮＦα活性进行了测定。结果表明，慢性肝炎患者ＩＬ－１、ＩＬ－８及ＴＮＦα活性分别为１５３８．３±３８６．５ｐｇ／ｍｌ，５０６．５±１３１．３ｐｇ／ｍｌ及２１２．６±９８．４ｐｇ／ｍｌ，明显高于对照组（Ｐ＜０．０１）；肝炎性肝硬化患者ＩＬ－１、ＩＬ－８及ＴＮＦα活性分别为２１６２．８±４３６．６ｐｇ／ｍｌ，６８２．６±２０４．５ｐｇ／ｍｌ及２４１．５±１０９．６ｐｇ／ｍｌ，明显高于对照组（Ｐ＜０．０１）；原发性肝癌患者ＩＬ－１、ＩＬ－８活性分别为６３２．６±１０７．６ｐｇ／ｍｌ，３１２．８±９５．８ｐｇ／ｍｌ，与对照组比较，ＩＬ－１活性明显升高（Ｐ＜０．０５），ＩＬ－８活性程度升高，但无明显差异（Ｐ＞０．０５）ＴＮＦα活性为３２１．６±１８３．２ｐｇ／ｍｌ，明显高于对照组。亦对上述３种细胞因子与慢性肝炎、肝硬化发生发展关系进行了初步分析与探讨。     

慢性肾炎患者sIL－2R水平、IL－2活性及mIL－2R表达的观察

本文应用ＥＬＩＳＡ法检测了４０例慢性肾小球肾炎血清可溶性白细胞介素２受体水平，同时对患者外周血单个核细胞膜白细胞介素２受体表达及白细胞介素２活性进行观察。结果患者ｓＩＬ－２Ｒ水平为６３４．８±１４２．９ｕ／ｍｌ，高于正常人２９５．０±１６５．７ｕ／ｍｌ，Ｐ＜０．００１；ｍＩＬ－２Ｒ阳性率为２５．６±４．３％，低于正常人４５．５±５．２％，Ｐ＜０．００１；ＩＬ－２活性为２．８５±１．６１ｕ／ｍｌ，低于正常人７．０６±４．５３ｕ／ｍｌ，Ｐ＜０．００１。并且ｓＩＬ－２Ｒ与ＢＵＮ呈正相关，ｒ＝０．４７０，Ｐ＜０．０２。提示慢性肾小球肾炎患者细胞免疫功能降低，且与肾功能损伤程度有关。     

Interleukin-1, Interleukin-1 Receptors and Interleukin-1 Receptor Antagonist

IL-1 (IL-1α or IL-1β) is the prototypic “multifunctional” cytokine. Unlike the lymphocyte and colony stimulating growth factors, IL-1 affects nearly every cell type, and often in concert with other cytokines or small mediator molecules. Although some lymphocyte and colony stimulating growth factors may be therapeutically useful, IL-1 is a highly inflammatory cytokine and the margin between clinical benefit and unacceptable toxicity in humans is exceedingly narrow. In contrast, agents that reduce the production and/or activity of IL-1 are likely to have an impact on clinical medicine. In support of this concept, there is growing evidence that the production and activity of IL-1, particularly IL-1β, are tightly regulated events as if nature has placed specific “road blocks” to reduce the response to IL-1 during disease. In addition to controlling gene expression, synthesis and secretion, this regulation extends to surface receptors, soluble receptors and a receptor antagonist. Investigators have studied how production of the different members of the IL-1 family is controlled, the various biological activities of IL-1, the distinct and various functions of the IL-1 receptor (IL-1R) family and the complexity of intracellular signaling. Mice deficient in IL-1β, IL-1β converting enzyme (ICE) and IL-1R type I have also been studied. Humans have been injected with IL-1 (either IL-1α or IL-1β) for enhancing bone marrow recovery and for cancer treatment. The IL-1 specific receptor antagonist (IL-IRa) has also been tested in clinical trials.     

Interleukin-11

Interleukin-11 (IL-11) is a cytokine which interacts with a variety of haemopoietic and non-haemopoietic cell types. Recombinant human IL-11 (rhIL-11; oprelvekin) is produced in Escherichia coli and differs from the naturally occurring protein only in the absence of the amino-terminal proline residue. In synergy with other factors, rhIL-11 stimulates the growth of myeloid, erythroid, and megakaryocyte progenitor cells in vitro. In vivo, rhIL-11 is active in mice, rats, dogs, guinea pigs, hamsters and non-human primates, where the principal activity measured was stimulation of megakaryocytopoiesis and thrombopoiesis. rhIL-11 has shown benefit in 2 clinical trials by significantly reducing severe chemotherapy-induced thrombocytopenia. In addition to its thrombopoietic activity, rhIL-11 has also shown activity in models of acute gastrointestinal mucosal damage. rhIL-11 enhanced survival in mice following cytoablative therapy and in a hamster model of chemotherapy-induced oral mucositis, where treatment with rhIL-11 was associated with decreased mucosal damage, accelerated healing and reduced numbers of deaths. rhIL-11 is currently in clinical trials for the treatment of chemotherapy-induced mucositis. In rat models of acute colonic injury and inflammatory bowel disease, rhIL-11 treatment reduced intestinal mucosal damage and alleviated clinical signs. rhIL-11 has direct effects on activated macrophages to reduce the production of pro-inflammatory mediators. In animal models of endotoxaemia, rhIL-11 treatment reduced serum levels of pro-inflammatory cytokines and blocked hypotension. rhIL-11 increased survival in models of Gram-negative sepsis and toxic shock. Based on these studies, rhIL-11 is currently in clinical trials for treatment of Crohn's disease. Other inflammatory conditions are being further evaluated. Mechanistically, rhIL-11 functions at many levels to control inflammation, ameliorate tissue damage and maintain haemostasis in the face of trauma or infection. rhIL-11 has direct effects on hepatocytes, inducing the production of acute phase reactant proteins, haem oxygenase and tissue inhibitor of metalloproteinase-1 (TIMP-1). TIMP-1 expression can also be induced in synoviocytes and chondrocytes by treatment with rhIL-11. rhIL-11 administration has been associated with increased plasma levels of von Willebrand factor and fibrinogen. rhIL-11 treatment potentially offers multiple benefits for cancer chemotherapy patients, such as prevention of thrombocytopenia, gastrointestinal epithelial protection and subsequent reduction of mucositis, and amelioration of inflammatory complications. In addition, rhIL-11 is being evaluated further in the treatment of inflammatory disorders such as inflammatory bowel disease, rheumatoid arthritis and sepsis.     

Interleukin-18

Interleukin-18 (IL-18), a recently described member of the IL-1 cytokine superfamily, is now recognized as an important regulator of innate and acquired immune responses. IL-18 is expressed at sites of chronic inflammation, in autoimmune diseases, in a variety of cancers, and in the context of numerous infectious diseases. This short review will describe the basic biology of IL-18 and thereafter address its potential effector and regulatory role in several human disease states including autoimmunity and infection. IL-18, previously known as interferon-gamma (IFN-gamma)-inducing factor, was identified as an endotoxin-induced serum factor that stimulated IFN-gamma production by murine splenocytes [(1) ]. IL-18 was cloned from a murine liver cell cDNA library generated from animals primed with heat-killed Propionibacterium acnes and subsequently challenged with lipopolysaccharide [(2) ]. Nucleotide sequencing of murine IL-18 predicted a precursor polypeptide of 192 amino acids lacking a conventional signal peptide and a mature protein of 157 amino acids. Subsequent cloning of human IL-18 cDNA revealed 65% homology with murine IL-18 [(3) ] and showed that both contain an unusual leader sequence consisting of 35 amino acids at their N terminus.     

Interleukin-3

Synopsis

Interleukin-3 is an early- and late-acting haemopoietic growth factor which promotes the proliferation and differentiation of multilineage and single lineage committed progenitor cells. It also has modulatory effects on mature cells, including basophils, monocytes and eosinophils. Interleukin-3 stimulates the proliferation of bone marrow and peripheral blood progenitor cells and increases bone marrow cellularity, causing a shift of haemopoiesis to the left, with a subsequent increase in the proportion of immature haemopoietic cells and in numbers of megakaryocytes and eosinophils. Interleukin-3 also potentiates granulocyte-macrophage colony-stimulating factor- (GM-CSF) and granulocyte colony-stimulating factor- (G-CSF) mediated mobilisation of peripheral blood progenitor cells from the bone marrow to the blood. Preliminary clinical trials show that recombinant human interleukin-3 (referred to as interleukin-3) reduces haematological toxicity in patients following standard- or high-dose chemotherapy with or without autologous bone marrow transplantation. The duration of neutropenia was reduced and importantly, platelet numbers were generally increased such that the duration of thrombocytopenia was also reduced in the majority of studies. There was a trend towards a lower requirement for platelet transfusions in treatment cycles that included interleukin-3 compared with those that did not, and the need to postpone further chemotherapy cycles due to prolonged haematological toxicity was reduced with interleukin-3. Sequential combination therapy with interleukin-3 followed by recombinant GM-CSF appears to further enhance haemopoietic recovery in these indications. Other potential applications of interleukin-3 include disease states with intrinsic bone marrow dysfunction, such as myelodysplasia and aplastic anaemia. Thus, the ability of interleukin-3 to reduce both neutropenia and thrombocytopenia in preliminary studies suggests that this cytokine will be useful, either alone or in sequential combination with other cytokines, for the treatment of haematological toxicity associated with chemotherapy, following bone marrow transplantation, and in the treatment of haemopoietic stem cell disorders.

Pharmacological Properties

Interleukin-3 (multipotential colony-stimulating factor) is a haemopoietic growth factor, secreted predominantly by activated T-helper lymphocytes. It stimulates the proliferation of early haemopoietic progenitor cells in the bone marrow, including colony-forming unit (CFU)-granulocyte-erythroid-macrophage-megakaryocyte (CFU-GEMM), CFU-granulocyte-macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), CFU-eosinophil (CFU-Eo), CFU-megakaryocyte (CFU-Meg), and CFU-basophil (Bas) cells. It also stimulates the proliferation of peripheral blood progenitor cells in vitro. Bone marrow cellularity is increased by interleukin-3 in patients with normal haemopoiesis, bone marrow failure or myelodysplastic syndrome, and there is a shift of haemopoiesis to the left, increasing the proportion of immature haemopoietic progenitor cells and the numbers of eosinophils and megakaryocytes. The cytokine also affects cells at later stages of maturation including basophils, eosinophils and monocytes. It is unclear whether interleukin-3 can induce the mobilisation of peripheral blood progenitor cells when administered alone; however, it potentiates the effect of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and recombinant granulocyte colony-stimulating factor (rG-CSF). In vitro studies indicate that interleukin-3 enhances the cytotoxic effects of cytarabine (ara-C) on acute myeloid leukaemia cells; however, its efficacy in humans in this setting remains to be determined. Data on the pharmacokinetic properties of recombinant human interleukin-3 are limited. Peak plasma concentrations are reached within 2 to 4 hours following subcutaneous administration of interleukin-3 and are dose-proportional. The plasma elimination half-life is 1.3 to 3.3 hours following subcutaneous administration and 0.4 to 1 hour following intravenous administration. The apparent systemic clearance of interleukin-3 is 0.3 L/h/kg, irrespective of the route of administration or dosage.

Clinical Potential

Recombinant human interleukin-3 (referred to as interleukin-3) has shown clinical efficacy in reducing haematological toxicity following standard- and high-dose chemotherapy treatment regimens in small phase I/II clinical trials reported to date. A daily dosage of 5 to 10 μg/kg, administered either subcutaneously or by continuous intravenous infusion, caused a significant increase in neutrophil and platelet counts after chemotherapy and reduced the duration of neutropenia and thrombocytopenia compared to that observed in control chemotherapy cycles in which interleukin-3 was not given. A reduction in the need to postpone further chemotherapy due to prolonged haematological toxicity was observed with interleukin-3 treatment, and the number of patients requiring platelet transfusions was also reduced. Sequential administration of interleukin-3 followed by rGM-CSF or rG-CSF may further reduce myelosuppression. Interleukin-3 also enhanced platelet and neutrophil recovery following autologous bone marrow transplantation, and in patients with bone marrow failure. Its relative benefits in reducing myelosuppression compared with those of other cytokines remain unclear. Preliminary findings indicate that sequential combination therapy with interleukin-3 and rGM-CSF may be beneficial compared with monotherapy with either agent in these indications. In addition, interleukin-3/rG-CSF-induced mobilisation of peripheral blood progenitor cells prior to apheresis and re-transplantation, or in vitro incubation of patients’ bone marrow cells with interleukin-3 and rGM-CSF or rG-CSF prior to transplantation, both appeared to enhance marrow recovery of platelet numbers. These findings require further investigation. Interleukin-3 may also offer some clinical benefit to patients with myelodysplastic syndromes in that their leucocyte counts are increased. However, it has shown only transient effects, if any, on platelet counts in these patients. Initial findings indicate that patients with aplastic anaemia may also derive some clinical benefit from treatment with interleukin-3. Further study of its efficacy relative to that of other agents in these indications is warranted.

Tolerability

There are few tolerability data available for interleukin-3. While adverse events have been reported frequently, they have been generally tolerable at dosages ≤ 10 μg/kg/day. Influenza-like symptoms (myalgia, arthralgia, fatigue), headache, and low grade fever have occurred most frequently. Severe headache occurring at dosages > 10 μg/kg/day was often a dose-limiting event. Other adverse events have included nausea, vomiting, skin rash, mild local erythema at the injection site, flushing, oedema, facial erythema, diarrhoea, rigors, malaise and dyspnoea; these were generally mild and resolved at the end of treatment. The tolerability profile of interleukin-3 appeared similar when the drug was administered prior to or following chemotherapy, and during combined sequential treatment with rGM-CSF or rG-CSF.

Dosage and Administration

In clinical trials, interleukin-3 has been administered once daily by subcutaneous injection or by continuous intravenous infusion. For the treatment of myelosuppression following chemotherapy, ≥ 5 μg/kg/day for 7 to 14 days appears to be an effective dosage, and 10 μg/kg/day has shown efficacy in patients following autologous bone marrow transplantation. A lower dosage of interleukin-3 2.5 μg/kg/day for 10 days followed by rGM-CSF therapy has also shown efficacy in the bone marrow transplantation setting. Interleukin-3 30 to 500 μg/m²/day for 15 days induced a haematological response in patients with bone marrow failure, and 250 to 500 μg/m²/day for 14 to 15 days induced a response in patients with myelodysplastic syndromes or aplastic anaemia.     

Interleukin-17

The particular interest of IL-17, a homodimeric cytokine of about 32kDa, is the strict requirement for an activation signal to induce its expression from a rather restricted set of cells, human memory T cells or mouse αβTCR⁺CD4^?CD8^? thymocytes. In contrast with the tightly controlled expression pattern of this gene, the IL-17 receptor, a novel cytokine receptor, is ubiquitously distributed but apparently more abundant in spleen and kidney. In addition to its capture by the T lymphotropic Herpesvirus Saimiri (HVS), this cytokine is inducing the secretion of IL-6, IL-8, PGE₂, MCP-1 and G-CSF by adherent cells like fibroblasts, keratinocytes, epithelial and endothelial cells. IL-17 is also able to induce ICAM-1 surface expression, proliferation of T cells, and growth and differentiation of CD34⁺ human progenitors into neutrophils when cocultured in presence of irradiated fibroblasts. In vitro, IL-17 synergjzes with other proinflammatory signals like TNFα for GM-CSF induction, and with CD40-ligand for IL-6, IL-8, RANTES and MCP-1 secretion from kidney epithelial cells. In vivo, injection of IL-17 induces a neutrophilia, except in IL-6-KO mice. The involvement of IL-17 in rejection of kidney graft has also been demonstrated. The role of this T cell secreted factor in various inflammatory processes is presently investigated.     

Interleukin-13

Gastrointestinal nematode parasites are one of the most prevalent types of infection worldwide. Evidence from both laboratory and human systems indicates that when resistance is evident immunity is mediated by effector mechanisms controlled by Thelper 2 type responses. Moreover, more recent evidence implicates a central role for interleukin 13. We raise the possibility that gut dwelling nematodes may have been an important driving force in the development of Th 2 responses involving IL-13. Moreover, that these parasites have evolved a variety of strategies to avoid destruction and to regulate any potential pathology associated with chronic infection.     

Interleukin-10

Interleukin-10 (IL-10) is a potent anti-inflammatory and immunosuppressive cytokine secreted by several cell types. Most anti-inflammatory effects of IL-10 are caused by its ability to deactivate macrophages and monocytes, whereas its immunosuppressive properties are due to functional inhibition of both antigen-presenting cells and T cells. On the other hand, IL-10 also exerts immunostimulatory effects, especially on B cells, CD8+ cytotoxic T cells and natural killer cells. In vivo administration of recombinant IL-10 (rIL-10) efficiently prevents experimental septic shock induced by endotoxin, staphylococcal superantigen or cecal ligation and puncture, as well as experimental autoimmune diseases mediated by T helper type 1 (T(H)1) cells and other inflammatory disorders. rIL-10 exerts paradoxical effects in cancer models, where it promotes tumour rejection, probably due to its stimulatory properties on cytotoxic cells. On the other hand, rIL-10 increases the severity of experimental infections caused by fungi or bacteria, and enhances systemic autoimmune features in mice with spontaneous lupus syndrome. Although the therapeutic potential of rIL-10 in human diseases seems promising, the multiple facets of rIL-10 in experimental immunopathology indicate that the success of clinical trials with rIL-10 will depend both on the appropriate selection of the patient populations to be treated and on the early detection of possible adverse effects.