IL-12p40 and IL-18 in crescentic glomerulonephritis: IL-12p40 is the key Th1-defining cytokine chain, whereas IL-18 promotes local inflammation and leukocyte recruitment.

Experimental crescentic glomerulonephritis (GN) is characterized by T helper 1 (Th1) directed nephritogenic immune responses and cell-mediated glomerular injury. IL-12p40, the common cytokine chain for both IL-12 and IL-23, is important in the generation and potentially the maintenance of Th1 responses, whereas IL-18 is a co-factor for Th1 responses that may have systemic and local proinflammatory effects. For testing the hypothesis that both endogenous IL-12p40 and endogenous IL-18 play pathogenetic roles in crescentic GN, accelerated anti-glomerular basement membrane GN was induced in mice genetically deficient in IL-12p40 (IL-12p40-/-), IL-18 (IL-18-/-), or both IL-12p40 and IL-18 (IL-12p40-/-IL-18-/-).

Experimental autoimmune Goodpasture's disease: a pathogenetic role for both effector cells and antibody in injury.

Background: Goodpasture's disease [antiglomerular basement membrane (GBM) glomerulonephritis] is a classic autoimmune disease and the only organ-specific autoimmune renal disease in which the antigen is well described. The importance of antibodies against the non-collagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] is well established. However, observational human studies and studies in experimental systems also imply a role for cell-mediated effector injury.

Direct-to-consumer advertising: developing evidence-based policy to improve retention and comprehension.

Pharmaceutical advertising was historically directed toward health care professionals and mainly communicated through medical journals. The arrival of direct-to-consumer advertising has sparked both praise and criticism. Although current Food and Drug Administration requirements for drug promotion were written from a health care professional perspective, the same regulations have been applied to advertising directed at consumers.

Endogenous IL-13 limits humoral responses and injury in experimental glomerulonephritis but does not regulate Th1 cell-mediated crescentic glomerulonephritis.

IL-13 is produced by T helper 2 (Th2) cells, has a role in stimulating Th2-mediated injury, alters humoral responses, and may directly suppress macrophage and neutrophil function. In immune renal disease, the engagement of different effector mediator systems, including humoral and cell-mediated effectors, can result in glomerular injury. Experimental crescentic glomerulonephritis (known as autologous anti-glomerular basement membrane glomerulonephritis) induced by planting an antigen in glomeruli of mice is Th1 directed, delayed-type hypersensitivity (DTH)-like, and antibody independent.

Fibrin independent proinflammatory effects of tissue factor in experimental crescentic glomerulonephritis.

Background: Tissue factor initiated glomerular fibrin deposition is an important mediator of injury in crescentic glomerulonephritis. Recent data have suggested noncoagulant roles for tissue factor in inflammation.

Methods: To test the hypothesis that in addition to its effects in initiating coagulation, tissue factor has proinflammatory effects in glomerulonephritis, rabbits given crescentic anti-glomerular basement membrane (GBM) antibody-induced glomerulonephritis were defibrinogenated with ancrod.

Experimental autoimmune anti-glomerular basement membrane glomerulonephritis: a protective role for IFN-gamma.

IL-12 and IFN-gamma play key roles in murine lupus and planted antigen models of glomerulonephritis. However, their roles in renal organ-specific autoimmunity are unknown. To establish the roles of endogenous IFN-gamma and IL-12 in experimental autoimmune anti-glomerular basement membrane (GBM) glomerulonephritis (EAG), EAG was induced in normal C57BL/6 mice (WT), IL-12p40-deficient (IL-12p40-/-) mice, and IFN-gamma-deficient (IFN-gamma-/-) mice by immunization with alpha3-alpha5(IV)NC1 heterodimers.

An IL-12-independent role for CD40-CD154 in mediating effector responses: studies in cell-mediated glomerulonephritis and dermal delayed-type hypersensitivity.

Crescentic glomerulonephritis (GN) results from IL-12-driven Th1-directed cell-mediated responses (akin to delayed-type hypersensitivity (DTH)) directed against glomerular Ags. CD40-CD154 interactions are critical for IL-12 production and Th1 polarization of immune responses. Crescentic anti-glomerular basement membrane GN was induced in C57BL/6 (wild-type (WT)) mice (sensitized to sheep globulin) by planting this Ag (as sheep anti-mouse glomerular basement membrane globulin) in their glomeruli.

Ex vivo lymphocyte proliferative function is severely inhibited in renal transplant patients on mycophenolate mofetil treatment.

Mycophenolate mofetil (MMF) is a recently introduced immunosuppressive drug. Its active form is mycophenolic acid (MPA). MPA specifically inhibits de novo purine synthesis, which is vital for T and B lymphocyte proliferation.

Leukocyte-derived interleukin-1beta interacts with renal interleukin-1 receptor I to promote renal tumor necrosis factor and glomerular injury in murine crescentic glomerulonephritis.

The involvement of proinflammatory cytokines interleukin (IL)-1 and tumor necrosis factor (TNF) in crescentic glomerulonephritis (GN) is well established. Recently the requirement of intrinsic renal cell participation via their production of TNF in crescentic GN was demonstrated. The current studies address the relative contributions of leukocyte and intrinsic renal cell-derived IL-1beta in the induction of TNF production and glomerular injury by studying bone marrow chimeric mice.

Contributions of IL-1beta and IL-1alpha to crescentic glomerulonephritis in mice.

ABSTRACT. Interleukin-1 (IL-1) is a pleiotropic proinflammatory cytokine with two distinct isoforms (IL-1alpha and IL-1beta) that signal through the same IL-1 type I receptor (IL-1RI). Contributions of IL-1beta have been demonstrated in human and experimental proliferative glomerulonephritis (GN), but the involvement of IL-1alpha has received little attention.

The role of flow cytometric ANCA detection in screening for acute pauci-immune crescentic glomerulonephritis.

Background: Most cases of pauci-immune crescentic glomerulonephritis (PICGN) are associated with serum anti-neutrophil cytoplasmic antibodies (ANCA). This article studied the sensitivity and specificity of serum ANCA, determined by flow cytometry and indirect immunofluorescence (IIF), to identify patients with acute PICGN.

Methods: 577 adults presenting for first biopsy of their native kidneys with serum taken for ANCA (flow cytometry and IIF) determination were studied.

Intrinsic renal cell expression of CD40 directs Th1 effectors inducing experimental crescentic glomerulonephritis.

Evidence suggests that human and experimental crescentic GN results from Th1-predominant immunity to glomerular antigens. CD40/CD154 signaling plays a key role in initiating Th1 responses and may direct Th1 effector responses. The role of CD40 in the development of GN was assessed in murine experimental anti-glomerular basement membrane GN.

Intrinsic renal cells are the major source of tumor necrosis factor contributing to renal injury in murine crescentic glomerulonephritis.

Macrophages are prominent participants in crescentic glomerulonephritis (GN) and have been suggested to be the major source of TNF in this cell-mediated form of glomerular inflammation. Intrinsic renal cells also have the capacity to produce TNF. For dissecting the contribution of local versus bone marrow (BM)-derived TNF in inflammatory renal injury, TNF chimeric mice were created by transplanting normal wild-type (WT) BM into irradiated TNF-deficient recipients (WT-->TNF-/- chimeras) and vice versa (TNF-/- -->WT chimeras).

T cells in glomerulonephritis.

The involvement of immunoglobulin and complement in glomerulonephritis has been recognized for many decades, but the involvement of sensitized T cells and the contributions of cellular immunity have only recently been appreciated. The relative contributions of humoral and cellular immunity in the immunopathogenesis may be an important determinant of the various histological patterns and clinical features of human glomerulonephritis. Subsets of T helper cells, Th1 and Th2, induce immune activation with distinct patterns of involvement of immunoglobulin isotypes and cellular immune effectors.

Plasminogen activator inhibitor-1 is a significant determinant of renal injury in experimental crescentic glomerulonephritis.

Crescentic glomerulonephritis is characterized by glomerular fibrin deposition, and experimental crescentic glomerulonephritis has been shown to be fibrin-dependent. Net fibrin deposition is a balance between activation of the coagulation system causing glomerular fibrin deposition and fibrin removal by the plasminogen-plasmin (fibrinolytic) system. Plasminogen activator inhibitor-1 (PAI-1) inhibits fibrinolysis by inhibiting plasminogen activators and has effects on leukocyte recruitment and matrix deposition.

Laboratory assessment of immune function in renal transplant patients.

Background: Advances in immunosuppression have made renal transplantation an effective therapy for end stage renal failure; with low rejection rates and long graft survival times. However, the major adverse consequences, infection and malignancy have not diminished. To predict this risk a score of immune competence has been developed from the simultaneous laboratory assessment of multiple parameters of immune function.

Adaptive immunity to nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae (NTHi) colonizes the upper respiratory tract of most healthy people and is also a major cause of infection in chronic obstructive lung disease. The immune response to this bacterium has not been well characterized. We tested the hypothesis that recurrent airway infection with NTHi may be associated with nonclearing adaptive immunity.

Effects of CTLA4-Fc on glomerular injury in humorally-mediated glomerulonephritis in BALB/c mice.

The effect of cytotoxic T-lymphocyte-associated molecule 4-immunoglobulin fusion protein (CTLA4-Fc) on humorally-mediated glomerulonephritis was studied in accelerated anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in BALB/c mice. This strain of mice develops antibody and complement dependent glomerulonephritis under this protocol. Sensitized BALB/c mice developed high levels of circulating autologous antibody titres, intense glomerular deposition of mouse immunoglobulin and complement, significant proteinuria, renal impairment, significant glomerular necrosis and a minor component of crescent formation 10 days after challenge with a nephritogenic antigen (sheep anti-GBM globulin).

Interleukin-10 inhibits experimental mesangial proliferative glomerulonephritis.

Conflicting reports exist regarding the effects of interleukin-10 (IL-10) on mesangial cells. There have been reports of both proliferative and antiproliferative effects, and both proinflammatory and anti-inflammatory effects of IL-10 on mesangial cells. However, the potential for IL-10 to affect glomerulonephritis characterized by mesangial proliferation is not known.

Acute lithium intoxication.

We present a case of acute lithium intoxication in a 51-year-old woman on chronic lithium therapy. Her serum lithium level was 10.6 mmol/l 13 hours after ingestion and 5.

IFN-gamma production by intrinsic renal cells and bone marrow-derived cells is required for full expression of crescentic glomerulonephritis in mice.

The contribution of IFN-gamma from bone marrow (BM) and non-BM-derived cells to glomerular and cutaneous delayed-type hypersensitivity (DTH) was studied in mice. Chimeric IFN-gamma mice (IFN-gamma(+/+) BM chimera), in which IFN-gamma production was restricted to BM-derived cells, were created by transplanting normal C57BL/6 (wild-type (WT)) BM into irradiated IFN-gamma-deficient mice. BM IFN-gamma-deficient chimeric mice (IFN-gamma(-/-) BM chimera) were created by transplanting WT mice with IFN-gamma-deficient BM.

The requirement for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in leukocyte-mediated immune glomerular injury.

Proliferative glomerulonephritis in humans is characterized by the presence of leukocytes in glomeruli. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) can potentially stimulate or affect T cell, macrophage, and neutrophil function. To define the roles of GM-CSF and G-CSF in leukocyte-mediated glomerulonephritis, glomerular injury was studied in mice genetically deficient in either GM-CSF (GM-CSF -/- mice) or G-CSF (G-CSF -/- mice).

Interleukin-12 from intrinsic cells is an effector of renal injury in crescentic glomerulonephritis.

Interleukin-12 (IL-12) directs the cognate nephritogenic T helper type 1 responses that initiate renal injury in murine crescentic glomerulonephritis (GN). The recent demonstration of IL-12 production by intrinsic renal cells, including mesangial and proximal tubular cells, raises the possibility that IL-12 from nonimmune cells may contribute to inflammatory renal injury. To address this possibility, the development of sheep anti-mouse glomerular basement membrane globulin-induced crescentic GN was studied in C57BL/6 wild-type (WT), IL-12-deficient (IL-12 -/-), and IL-12 "chimeric" mice.