RESUMEN
Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.
Asunto(s)
Inhibidores de la Calcineurina , Trasplante de Órganos/efectos adversos , Dolor/inducido químicamente , Adulto , Huesos/diagnóstico por imagen , Huesos/fisiopatología , Ciclosporina/administración & dosificación , Ciclosporina/efectos adversos , Ciclosporina/sangre , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/sangre , Femenino , Pie , Trasplante de Corazón/efectos adversos , Humanos , Trasplante de Riñón/efectos adversos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Dolor/diagnóstico , Manejo del Dolor , Cintigrafía , Síndrome , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversos , Tacrolimus/sangreRESUMEN
BACKGROUND: Based on the observation of 7 patients with chronic IgA nephritis and on a course to end-stage renal failure after several years, D'Amico et al. [1993] reported on a "point of no return" at 2.5 to 3 mg/dl serum creatinine. After exceeding this limit all 7 patients exhibited an irreversible progressive renal failure. PATIENTS AND METHODS: Therefore, 115 patients with IgA nephritis from the "German Glomerulonephritis Therapy Study" were examined in order to look for the existence of such a "point of no return". RESULTS: Three different courses could be distinguished: a stable chronic course with constantly normal or only minor elevated serum creatinine lasting for years (91 patients), a progressive course with continuously increasing serum creatinine (22 patients), and a rare (only 2 patients) early acute course with a short-term increase of serum creatinine followed by a rapid return to the normal range. After exceeding 3 mg/dl serum creatinine no remissions were observed in the progressive cases. Sixteen patients showed a rapid, continuously progressive course until end-stage renal failure with exactly the same progression as the 7 patients of D'Amico et al. Six patients of the 22 progressors were not observed long enough. The serum creatinine level doubled on average from 3 to 6 mg/dl within 10 months. CONCLUSION: Our study confirmed the existence of a "point of no return" at 3 mg/dl (265 micromol/l) during the natural course of chronic IgA nephritis.
Asunto(s)
Creatinina/sangre , Glomerulonefritis por IGA/sangre , Adolescente , Adulto , Anciano , Enfermedad Crónica , Progresión de la Enfermedad , Femenino , Glomerulonefritis por IGA/complicaciones , Humanos , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Hydrogen peroxide (H2O2) is an important mediator of glomerular injury, which induces proliferation and cell contraction in mesangial cells. The aim of this study was to investigate whether and which ion currents are activated during the early cellular responses to H2O2, and to study possible mechanisms of their activation. METHODS: The effect of H2O2 on membrane voltage of mesangial cells in short-term culture was investigated with the patch clamp technique in the fast whole cell configuration. RESULTS: H2O2 contracted mesangial cells and induced a concentration-dependent biphasic membrane voltage response. One hundred micromol/liter H2O2 led to a hyperpolarization of mesangial cells from -45 +/- 1 to -55 +/- 1 mV, which was followed by a sustained depolarization to -20 +/- 3 mV. The hyperpolarization induced by H2O2 was completely blocked by the K+ channel blocker Ba2+. In the presence of a low extracellular Cl- concentration (32 mmol/liter), the depolarization induced by H2O2 was significantly increased. The H2O2-induced depolarization was inhibited by 100 micromol/liter of the disulfide-reducing agent dithiothreitol, whereas higher concentrations of dithiothreitol (1 mmol/liter) were required to partially inhibit the hyperpolarization. Protein kinase C inhibitors blocked the H2O2-induced depolarization, but not the hyperpolarization. CONCLUSIONS: The data indicate that H2O2 leads to a biphasic membrane voltage response in mesangial cells: an initial transient hyperpolarization, which is due to the activation of a K+ conductance, and a subsequent depolarization, which is, at least in part, due to the activation of a Cl- conductance. The oxidation of thiol groups by H2O2 is involved in the membrane voltage response, and the depolarization may be regulated by protein kinase C.
Asunto(s)
Mesangio Glomerular/efectos de los fármacos , Mesangio Glomerular/fisiología , Peróxido de Hidrógeno/farmacología , Oxidantes/farmacología , Animales , Calcio/metabolismo , Células Cultivadas , Cloruros/metabolismo , Diamida/farmacología , Ditiotreitol/farmacología , Conductividad Eléctrica , Inhibidores Enzimáticos/farmacología , Espacio Extracelular/metabolismo , Mesangio Glomerular/citología , Iones , Potasio/fisiología , Proteína Quinasa C/antagonistas & inhibidores , Ácido Pirúvico/farmacología , Ratas , Reactivos de Sulfhidrilo/farmacologíaRESUMEN
BACKGROUND: Patients on chronic hemodialysis treatment are at elevated atherogenic risk, and dyslipidemia appears to be one of the major risk factors. However, most of these patients exhibit elevated serum triglycerides, whereas serum cholesterol and low-density lipoprotein (LDL) cholesterol levels are in the normal range. This study was therefore designed to examine the influence of hypertriglyceridemia under the condition of hemodialysis and diabetes mellitus on LDL metabolism. METHODS: LDL was isolated from healthy controls, hypertriglyceridemic diabetic patients, and nondiabetic hemodialysis patients (N = 30, 10 in each group), which were separated into six subfractions by density gradient ultracentrifugation and were characterized concerning lipid/protein composition, degree of glycation, and oxidation. Uptake of 125I-labeled LDL was examined via LDL receptors of HepG2 cells and scavenger receptors of mouse peritoneal macrophages. RESULTS: In hemodialysis patients, serum triglycerides were significantly elevated, whereas cholesterol levels were within the normal range. Triglyceride enrichment occurred in the very low-density lipoprotein (VLDL) class and LDL class, and an accumulation of a highly atherogenic small dense LDL subfraction could be detected predominantly in patients with non-insulin-dependent diabetes mellitus. LDL of hemodialysis patients also contained elevated levels of lipid peroxidation products, which were even higher in diabetic patients. Alterations in composition, size, and configuration of LDL from diabetic and nondiabetic patients on hemodialysis impaired LDL receptor-mediated degradation and enhanced the uptake of these modified LDL particles via nonsaturable scavenger receptors. CONCLUSION: Diminished LDL receptor-mediated uptake of modified, triglyceride-rich, small dense LDL most likely leads to accumulation of these lipoproteins in vivo, favoring the development of atherosclerotic lesions. Future clinical studies must demonstrate whether patients will benefit from reducing these atherogenic particles by lipid-lowering intervention.
Asunto(s)
Lipoproteínas/metabolismo , Diálisis Renal , Apolipoproteínas B/metabolismo , Unión Competitiva , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Glicosilación , Humanos , Hipertrigliceridemia/sangre , Hipertrigliceridemia/complicaciones , Radioisótopos de Yodo , Peroxidación de Lípido , Lipoproteínas/sangre , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Triglicéridos/sangre , Células Tumorales CultivadasAsunto(s)
Acidosis/etiología , Adenocarcinoma/complicaciones , Neoplasias del Colon/complicaciones , Creatinina/sangre , Acidosis/fisiopatología , Adenocarcinoma/sangre , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Anciano , Neoplasias del Colon/sangre , Neoplasias del Colon/radioterapia , Neoplasias del Colon/cirugía , Humanos , MasculinoRESUMEN
Patients with diabetes mellitus undergoing chronic hemodialysis treatment have the worst outcome on dialysis due to an increased rate of cardiovascular complications. Nearly all patients present with dyslipidemia, a prominent vascular risk factor, probably responsible for the high rate of vascular injury. Since both uremia and diabetes predispose to hypertriglyceridemia, the present study was conducted to investigate the influence of diabetes mellitus and/or hypertriglyceridemia on lipoprotein metabolism in hemodialysis patients. LDL was isolated and characterized from hyper- and normotriglyceridemic diabetic and nondiabetic hemodialysis patients (n = 40; 10 in each group); also, LDL-receptor-dependent uptake and intracellular cholesterol metabolism were studied in HepG2 cells. In addition, scavenger-receptor-mediated uptake was examined in mouse peritoneal macrophages. LDL isolated from nondiabetic normotriglyceridemic hemodialysis patients exhibited impaired cellular uptake via the LDL receptor. Additionally, intracellular sterol synthesis was less inhibited and cholesterol esterification was reduced compared with LDL from healthy control subjects. Reduction of catabolic capacities was more marked in hemodialysis patients who were either diabetic or hypertriglyceridemic and even more pronounced in patients presenting with a combination of both diabetes and hypertriglyceridemia. Hypertriglyceridemic and diabetic patients showed reduced lipase activity and increased LDL oxidation. Furthermore, they accumulated a fraction of small, dense LDL, and LDL was predominantly taken up via the scavenger-receptor pathway in peritoneal macrophages. This study elucidates the distinct influence of diabetes and/or hypertriglyceridemia in hemodialysis patients on cellular LDL metabolism via specific and nonspecific metabolic pathways. Furthermore, it underscores the cumulative impact of these pathologic entities on impairment of lipoprotein metabolism and increase of cardiovascular risk.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Hipertrigliceridemia/metabolismo , Lipoproteínas/metabolismo , Diálisis Renal , Anciano , Animales , Apolipoproteínas B/sangre , Ésteres del Colesterol/biosíntesis , Femenino , Humanos , Lipasa/sangre , Lípidos/sangre , Lípidos/clasificación , Lipoproteínas LDL/sangre , Lipoproteínas LDL/química , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacología , Hígado/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Oxidación-Reducción , Esteroles/biosíntesis , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
Studies on human macrophages are restricted due to difficulties in isolating significant numbers of human macrophages. High numbers of monocytes/macrophages can be obtained from peritonitis effluents of patients treated with peritoneal dialysis. To determine whether these cells might be useful for functional studies, we characterized peritoneal macrophages (PM) immediately after isolation from the dialysate effluents and their subsequent differentiation. During a 10 days culture period they differentiated morphologically and phenotypically (FACS-analysis) from monocyte-like cells to macrophages. Reflecting the intraperitoneal inflammation we found protein- and mRNA-synthesis of IL-8 and monocyte-chemoattractant-protein-1 (MCP-1) to be upregulated in PM after isolation from the effluents. In contrast, TNF-alpha was downregulated and could not be stimulated by LPS and/or IFN-gamma, reflecting the phenomenon of desensitization. After 10 days in culture, cytokine production normalized to a constitutive level and the TNF-alpha responsiveness to LPS was restored. These data suggest the recovery of PM from the inflammatory prestimulation. Therefore PM harvested from peritoneal dialysis effluents might provide a useful tool for further studies on the role of human macrophages in inflammation.
Asunto(s)
Macrófagos Peritoneales/citología , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritonitis/patología , Diferenciación Celular , Separación Celular , Células Cultivadas , Quimiocina CCL2/biosíntesis , Humanos , Interferón gamma/farmacología , Interleucina-8/biosíntesis , Lipopolisacáridos/farmacología , Activación de Macrófagos , ARN Mensajero/biosíntesis , Receptores de Superficie Celular/análisis , Factores de Tiempo , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genéticaAsunto(s)
Hipertensión/complicaciones , Hipertensión/cirugía , Bulbo Raquídeo/irrigación sanguínea , Bulbo Raquídeo/cirugía , Obstrucción de la Arteria Renal/complicaciones , Procedimientos Quirúrgicos Vasculares , Femenino , Humanos , Imagen por Resonancia Magnética , Bulbo Raquídeo/patología , Persona de Mediana EdadAsunto(s)
Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacocinética , Análisis de Varianza , Ciclosporina/uso terapéutico , Femenino , Humanos , Inmunosupresores/sangre , Trasplante de Riñón/fisiología , Tasa de Depuración Metabólica , Persona de Mediana Edad , Ácido Micofenólico/sangre , Ácido Micofenólico/uso terapéutico , Prednisona/uso terapéutico , Análisis de RegresiónRESUMEN
BACKGROUND: Osteopenia and osteoporosis are frequent complications after kidney transplantation. Data for the treatment of low bone mass after kidney transplantation are not available. METHODS: To test the efficacy of antiresorptive treatment, 46 patients with osteopenia or osteoporosis after kidney transplantation (bone mineral density < or =1.5 SD below normal) were randomly assigned to three groups cyclically treated as follows: group 1 with daily oral clodronate (800 mg) and group 2 with daily intranasal calcitonin (200 IU) for 2 weeks every 3 months. These two groups were compared with a control group (group 3). Every patient was supplemented with 500 mg of calcium per day. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) at the lumbar spine and femoral neck before and after the 12-month treatment period. RESULTS: BMD at the lumbar spine was increased by 4.6% in the clodronate group (n=15, P=0.005), by 3.2% in the calcitonin group (n=16, P=0.034), and by 1.8% in the control group (n=15, P=0.265). However, the differences in BMD changes among the groups were not statistically significant. During therapy, serum calcium decreased slightly in all groups by 4.6%; however, parathyroid hormone values increased significantly in the treatment groups by 116%. Therapy was well tolerated without impact on graft function. CONCLUSIONS: Cyclical therapy with clodronate or calcitonin appears to induce a gain in BMD at the lumbar spine in patients with low bone mass after kidney transplantation. This treatment had no adverse impact on graft function but may aggravate preexisting secondary hyperparathyroidism.
Asunto(s)
Enfermedades Óseas Metabólicas/tratamiento farmacológico , Enfermedades Óseas Metabólicas/etiología , Trasplante de Riñón , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Complicaciones Posoperatorias/terapia , Administración Intranasal , Administración Oral , Adulto , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/metabolismo , Calcitonina/uso terapéutico , Calcio/uso terapéutico , Ácido Clodrónico/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/metabolismo , Proyectos Piloto , Estudios Prospectivos , Caracteres SexualesAsunto(s)
Antiinflamatorios/uso terapéutico , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Prednisona/uso terapéutico , Fibrosis Retroperitoneal/tratamiento farmacológico , Adulto , Humanos , Masculino , Ácido Micofenólico/uso terapéutico , Fibrosis Retroperitoneal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del TratamientoAsunto(s)
Ciclosporina/sangre , Rechazo de Injerto/epidemiología , Inmunosupresores/sangre , Trasplante de Riñón/inmunología , Ácido Micofenólico/sangre , Suero Antilinfocítico/uso terapéutico , Creatinina/sangre , Ciclosporina/uso terapéutico , Infecciones por Citomegalovirus/epidemiología , Monitoreo de Drogas , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Trasplante de Riñón/fisiología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Complicaciones Posoperatorias/epidemiología , Esteroides/uso terapéutico , Factores de Tiempo , Infecciones Urinarias/epidemiologíaAsunto(s)
Enfermedades Óseas Metabólicas/tratamiento farmacológico , Calcitonina/uso terapéutico , Calcio/uso terapéutico , Ácido Clodrónico/uso terapéutico , Trasplante de Riñón/fisiología , Osteoporosis/tratamiento farmacológico , Dolor , Complicaciones Posoperatorias , Absorciometría de Fotón , Biomarcadores/sangre , Densidad Ósea , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/etiología , Osteoporosis/fisiopatología , Dimensión del DolorAsunto(s)
Inmunosupresores/farmacocinética , Trasplante de Riñón/inmunología , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacocinética , Análisis de Varianza , Creatinina/sangre , Humanos , Inmunosupresores/sangre , Inmunosupresores/uso terapéutico , Tasa de Depuración Metabólica , Ácido Micofenólico/sangre , Ácido Micofenólico/uso terapéutico , Análisis de Regresión , Factores de TiempoRESUMEN
Angiotensin II modulates cellular functions of podocytes. The aim of this study was to examine the effects of angiotensin II (Ang II) on membrane voltage (Vm) and cytosolic calcium activity ([Ca2+]i) of rat podocytes. To approach better the in vivo situation, we have developed an experimental approach that allows podocytes to be studied in the intact microdissected glomerulus. Ang II depolarized podocytes in the glomerulus (EC50 15 nM, N = 49). Like podocytes in the glomerulus, podocytes in short-term culture also depolarized in response to Ang II (10 nM, N = 5). Ang II increased [Ca2+]i in podocytes in culture (EC50 3 nM, N = 229). In a solution with reduced extracellular [Ca2+] (10 microM), Ang II-mediated [Ca2+]i increase was significantly reduced by 60% +/- 20% (N = 12). Flufenamate, an inhibitor of nonselective ion channels, inhibited Ang II-mediated increase of [Ca2+]i (IC50 20 microM, N = 29). The Ang subtype 1 (AT1) receptor antagonist losartan inhibited both Ang II-mediated depolarization and [Ca2+]i increase in podocytes (N = 5 to 35). Our results support the concept that Ang II might influence podocyte function directly via an AT1 receptor.
Asunto(s)
Angiotensina II/farmacología , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/fisiología , Animales , Calcio/metabolismo , Células Cultivadas , Electrofisiología , Glomérulos Renales/citología , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , RatasRESUMEN
AIM: The aim of this study was to investigate the influence of bradykinin on the intracellular calcium activity ([Ca2+]i) in human mesothelial cells in culture. RESULTS: Bradykinin (1-1000 nmol/l) caused a concentration-dependent and reversible increase of [Ca2+]i in mesothelial cells (n = 94); 10 nmol/l bradykinin increased [Ca2+]i from 23 +/- 9 to 670 +/- 170 nmol/l (n = 36). The pattern of the bradykinin-induced [Ca2+]i increase was biphasic with a transient [Ca2+]i peak, which was followed by a sustained [Ca2+]i plateau. The bradykinin-mediated [Ca2+]i plateau, but not the peak, was inhibited in a solution with an extracellular reduced Ca2+ concentration (from 1000 to 1 micromol/l, n = 11). Flufenamate (> or = 10 micromol/l), an inhibitor of non-selective ion channels abolished the bradykinin-mediated increase of [Ca2+], whereas the L-type Ca2+ channel blocker nicardipine (10 micromol/l) had no effect (n = 3-5). The [Ca2+]i response to bradykinin was inhibited by the BK2 antagonist Hoe 140 (IC50 +/- k7 nmol/l, n = 30). CONCLUSIONS: The data indicate that bradykinin stimulates [Ca2+]i in mesothelial cells by a release of Ca2+ from intracellular stores and an influx from Ca2+ through non-selective channels via a BK2 receptor.
Asunto(s)
Bradiquinina/farmacología , Calcio/metabolismo , Membranas Intracelulares/metabolismo , Peritoneo/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Células Cultivadas , Células Epiteliales/metabolismo , Epitelio/metabolismo , Espacio Extracelular/metabolismo , Ácido Flufenámico/farmacología , Humanos , Nicardipino/farmacología , Concentración Osmolar , Peritoneo/citología , Receptores de Bradiquinina/fisiologíaRESUMEN
A 28-year-old woman was kidney transplanted. She had an inapparent hepatitis B virus (HBV) infection 2 years previously. At the time of transplantation she was hepatitis B surface antigen (HBsAg) negative, anti-HBs, anti-HBc, anti-HBe and anti-HCV antibody positive and her transaminase activities were within the normal range. The donor of the kidney allograft was HBV negative. Twelve weeks after transplantation a life-threatening liver failure occurred with a rapid rise of alanine aminotransferase (ALT) to 1427 U/l and a decrease of the prothrombin time to 25% of normal value. Anti-HBs had become negative, anti-HBc and anti-HBe titers had decreased. HBsAg became positive, associated with a HBV DNA of 3 x 10(8) genome equivalents/ml. Azathioprine and prednisone were withdrawn and foscarnet therapy was started. This therapy led to a decrease of ALT activity associated with an elimination of HBsAg and HBV DNA. Eight months after transplantation liver function tests were within the normal range. Graft rejection did not occur despite low or intermittent cessation of immunosuppressive therapy.
Asunto(s)
Hepatitis B/etiología , Trasplante de Riñón/efectos adversos , Adulto , Femenino , Hepatitis B/diagnóstico , Hepatitis B/terapia , Humanos , RecurrenciaRESUMEN
BACKGROUND/AIMS: Transplant renal artery stenosis usually develops in the later period after renal transplantation and is usually due to atherosclerosis and fibrosis at the anastomosis. A kinking renal artery stenosis, however, is a rare cause of early graft dysfunction. METHODS: In a 34-year-old-man early graft failure developed within 1 week after kidney transplantation. In the presence of histologically proven ischemic damage an arterial kinking stenosis was diagnosed by color Doppler sonography. Selective arteriography confirmed the sharp kinking of the transplant renal artery; however, a significant stenosis could not be visualized by arteriography. RESULTS: Due to progressive loss of renal function surgical resection of scar tissue in the kink of the transplant artery and nephropexy was performed. Immediately thereafter graft function and blood pressure significantly improved so that the successful clinical outcome of this unusual case of early graft failure confirmed the relevance of the arterial kinking stenosis. CONCLUSIONS: In this unusual case of early graft dysfunction relevant kinking renal artery stenosis could not be adequately visualized by arteriography, although color Doppler sonography clearly demonstrated the stenosis. Therefore, both methods should be considered if parenchymal causes of graft dysfunction are excluded by biopsy and a kinking renal artery stenosis is suspected.
Asunto(s)
Trasplante de Riñón , Complicaciones Posoperatorias/etiología , Obstrucción de la Arteria Renal/complicaciones , Adulto , Supervivencia de Injerto , Humanos , Masculino , Complicaciones Posoperatorias/diagnóstico por imagen , Radiografía , Obstrucción de la Arteria Renal/diagnóstico por imagen , Factores de Tiempo , Ultrasonografía Doppler en ColorRESUMEN
BACKGROUND: Interleukin-8 and monocyte chemotactic protein-1 (MCP-1) are major leukocyte chemoattractants during bacterial peritonitis by recruiting neutrophils and monocytes/macrophages respectively. METHODS: Peritoneal macrophages (PM) from 12 different CAPD patients with peritonitis were stimulated with either 10 ng/ml LPS, 10 ng/ml IFN-gamma or LPS+IFN-gamma, and IL-8 and MCP-1 production was determined on protein and mRNA levels by using ELISA technique and Northern blot analysis. To obtain information from two different stages of activation, experiments were done with highly activated PM directly after isolation and with cells after 10 days in culture, each group being stimulated for 4 h. Unstimulated cells served as control. RESULTS: Immediately after isolation IL-8 mRNA-expression and synthesis was high and could be further increased by LPS stimulation, whereas IFN-gamma treatment showed no significant influence. The levels of MCP-1 were also initially high but could not be further stimulated by LPS, whereas addition of IFN-gamma resulted in a significant rise in MCP-1 synthesis. After 10 days in culture LPS-stimulation of cells again revealed a significant increase in IL 8 protein synthesis, whereas IFN-gamma showed no effect. LPS anergy for MCP-1 was still seen in PM after 10 days in culture, and IFN-gamma treatment again induced a significant rise in MCP-1 synthesis. The overall production of both chemokines was far higher on day 1 compared to day 10. CONCLUSION: Our data show differences in LPS/IFN-gamma regulation for IL-8 and MCP-1 in both highly activated and in resting, mature peritoneal macrophages, suggesting distinct pathways for these chemokines that may offer a means of control for the specific recruitment of neutrophils and monocytes/macrophages in bacterial peritonitis.