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S C Jordan

Publications and source records attributed to S C Jordan.

At least 55 records · Page 3Linked to original sources
PubMed1996

Delayed development of obliterative bronchiolitis syndrome with OKT3 after unilateral lung transplantation. A plea for multicenter immunosuppressive trials.

There is no consensus regarding the optimal induction immunosuppression regimen after lung transplantation (LT). In addition to the potential benefit of a reduced incidence of early acute allograft rejection, cytolytic induction immunosuppression may impact on long-term allograft function. We retrospectively assessed our incidence of obliterative bronchiolitis syndrome (OBS) stages Ia and IIa in LT survivors given two different cytolytic induction immunosuppression regimens: (between March 1989 and October 1990) OKT3 (5 mg/d)x10 to 14 days (n=11) vs (between November 1990 and April 1993) Minnesota antilymphocyte globulin (MALG) (10 to 15 mg/kgdx5 to 7 days. Cyclosporine (CSA) (whole blood polyclonal assay=600 to 800 ng/mL), azathioprine (1 to 2 mg/kg/d), and maintenance prednisone (0.2 mg/kg/d) were similar. Surveillance spirometry was performed monthly, in accordance with accepted American Thoracic Society criteria. Fiberoptic bronchoscopy with transbronchial biopsies (TBBs) were performed for clinical indications. Surveillance TBBs were not performed during the era of this study. As defined by the ISHLT "Working Formulation for the Standardization of Nomenclature and for Clinical Staging of Chronic Dysfunction in Lung Allografts," latencies to development of OBS stages Ia and IIa were determined by Kaplan-Meir analysis. Stepwise regression (Cox proportional hazards model) was performed for the variables: cytolytic induction regimen, episodes cytomegalovirus (CMV) pneumonitis, episodes CMV infection, serologic CMV donor (+): recipient (-) mismatch, prior pregnancy, HLA (A,B,DR +/- DQ) mismatches, episodes greater than grade A1 acute cellular rejection (ACR). We found that the OKT3 cohort experienced longer latencies for OBS stages Ia and IIa. Latencies to OBS stages Ia for OKT3 ve MALG were 962 +/- 65 vs 354 +/- 85 days (X +/- SEM) respectively. Brookmeyer-Crowley 95% confidence intervals for median latencies were 744 to 1,180 vs 266 to 510 days for OKT3 vs MALG, respectively. The Cox model was significant only for the variable of the induction cytolytic immunosuppression regimen (p=0.0015). By physiologic criteria, a longer course of OKT3 appeared superior to the short-course MALG protocol in delaying chronic lung allograft dysfunction. These effects may be related either to inherent differences in the antilymphocyte preparations or, alternatively, the difference in duration of treatment between groups. Surveillance TBB and treatment of detected occult ACR may serve to negate the observed differences in latencies for OBS.

Acute Disease↗
PubMed1995

Interleukin-12 mRNA levels in renal allograft fine-needle aspirates do not correlate with acute transplant rejection.

TH1 cytokines, including gamma-interferon (IFN), are critical in the initiation and progression of allograft rejection. As interleukin (IL)-12 up-regulates gamma-IFN, we assessed the role of IL-12 in human transplant rejection. Twenty renal allograft fine-needle aspirates from 19 patients were obtained, evaluated in the standard fashion, and assessed for gamma-IFN and IL-12p40 subunit mRNA levels using nested reverse transcriptase polymerase chain reaction. Ten aspirates demonstrated acute rejection by clinical criteria, and 9 of the 10 aspirates contained gamma-IFN while only 3 demonstrated IL-12; there were no distinguishing characteristics for these 3 patients with regard to therapy, or time of onset and severity of rejection. Seven patients without clinical or morphologic rejection failed to demonstrate gamma-IFN or IL-12. Three patients had discrepant findings; there was no morphologic rejection, yet all 3 patients contained gamma-IFN and 1 patient demonstrated rejection on subsequent biopsy. However, only 1 aspirate exhibited IL-12 and this patient had no documented subsequent rejection. This study confirms the association of gamma-IFN mRNA with acute rejection. In contrast, IL-12 mRNA does not appear to play a key role early in the rejection process.

Acute Disease↗
PubMed1995

Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation.

Lung transplantation is now routinely performed for a wide range of end-stage cardiopulmonary disorders. Despite overcoming the problems associated with early acute rejection, chronic rejection (CR) in the form of obliterative bronchiolitis has emerged as the primary cause of late graft loss. The mechanisms involved in the development of CR of lung allografts are poorly understood, and no effective therapy is currently available. To better understand the pathological events associated with CR and tolerance, we examined two models of lung allograft rejection established in our laboratory. First, we exchanged left lung allografts between moderately histoincompatible inbred rat strains (WKY-->F344: n = 42 and F344-->WKY: n = 40). The WKY-->F344 model was previously shown to develop spontaneous tolerance, while the converse model (F344-->WKY) showed persistent acute rejection. The purpose of this investigation was to assess histopathological changes associated with long-term grafts left in place up to 140 days after transplant. To confirm that tolerance had developed, skin-grafting experiments were performed. Five skin grafts from each strain were placed on lung allograft recipients on day 35 after transplant and skin allograft survival was assessed and compared with controls. Acute rejection (AR) was graded histologically (stage O-IV) and the pathologic intensity of inflammation and CR were graded (0-4: 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = 76-100%) on percentage of involvement with the following categories being examined: (a) lymphocytic infiltration (perivascular, peribronchial, and peribronchiolar) and (b) vasculitis, edema, hemorrhage, and necrosis. Finally, chronic rejection was diagnosed by the presence of intimal hyperplasia, interstitial fibrosis, peribronchiolar fibrosis, bronchiolitis obliterans, and bronchiectasis. The WKY-->F344 animals showed progressive AR (stage III, day 21). Thereafter, the AR subsided spontaneously and was stage 0 on day 140. There were no signs of CR in these animals. In the F344-->WKY model, the AR progressed up to stage III-IV (day 21) and maintained for several weeks at stage III. Thereafter, pictures of the lungs showed CR on days 49, 70, and 98. There were significant differences between the two models during the chronic phase, such as interstitial fibrosis (0 +/- 0 vs. 1.8 +/- 1.3, P < 0.005), peribronchiolar fibrosis (0 +/- 0 vs. 3.6 +/- 0.55, P < 0.01), vasculitis (0.2 +/- 0.45 vs. 2.0 +/- 0, P < 0.008), and intimal hyperplasia (0.2 +/- 0.45 vs. 2.6 +/- 0.9, P < 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Soluble CTLA4Ig modifies parameters of acute inflammation in rat lung allograft rejection without altering lymphocytic infiltration or transcription of key cytokines.

The efficacy of CTLA4Ig in blocking immune activation and allograft rejection (AR) was tested in an aggressive and rapid model of rat lung AR (Brown Norway [BN]-->Lewis [LEW]). CTLA4Ig is a recombinant soluble protein that binds with high affinity to rat B7/BB1 and other surface molecules on APCs, subsequently blocking the binding of B7/BB1 to CD28/CTLA4 on T cells. This interrupts the costimulatory pathway critical for complete T cell activation and completion of the AR process. Left single-lung transplants were performed between BN-->Lew. Five allograft recipients were examined in each group. At transplantation, animals received 250 micrograms of CTLA4Ig or 250 micrograms of control Ig intraperitoneally daily until sacrifice. Animals were sacrificed on days 2, 4, and 7 after transplant. Control (BN-->Lew) grafts show irreversible rejection by day 7. Syngeneic (Lew-->Lew) grafts show no AR on day 7. AR episodes were graded histologically (stages 0-IV) and pathologic intensity of inflammation was graded on percentage of involvement. Cytokine transcript levels were measured in control and CTLA4Ig-treated animals (n = 5 in each group) on day 7 using reverse transcriptase polymerase chain reaction techniques. The most profound differences were found on day 7 after transplant. The degree of lymphocytic infiltration was greater in the CTLA4Ig group (perivascular: 4 +/- 0 vs. 2.6 +/- 0.6, peribronchial: 4 +/- 0 vs. 2.2 +/- 0.4, and peribronchiolar: 3.6 +/- 0.5 vs. 2 +/- 0.3, P < 0.01). However, in striking contrast, the stage of AR (3 +/- 0 vs. 4 +/- 0, P < 0.01), vasculitis (1 +/- 0.7 vs. 2.6 +/- 0.6, P < 0.05), hemorrhage (0.4 +/- 0.6 vs. 3.2 +/- 0.4, P < 0.01), and necrosis (0 +/- 0 vs. 2.4 +/- 0.5, P < 0.005) were significantly reduced in animals treated with CTLA4Ig. Since CTLA4Ig blocks Th1 cell activation in vitro, we compared the levels of Th1 inflammatory cytokines IL-2, gamma-IFN, and TNF-alpha in the two models. The intragraft ratios (CTLA4Ig/control) were IL-2:0.77, gamma-IFN: 1.29, and TNF-alpha:1.33. Thus, CTLA4Ig did not significantly block intragraft production of Th1 cytokines on day 7.(ABSTRACT TRUNCATED AT 400 WORDS)

Abatacept↗
PubMed1995

Prevention of chronic rejection and graft arteriosclerosis by tolerance induction.

Chronic rejection is a major cause of graft failure in solid organ transplants after the first year. A characteristic lesion in a variety of chronically rejecting organs is a fibrointimal proliferative arteriosclerosis. It has been speculated that approaches to tolerance induction may be effective in obviating not only acute, but also chronic, rejection. A picture of chronic rejection develops naturally in heart grafts transplanted from the Lewis-to-F-344 strain of rat. We examined whether tolerance induction by bone marrow transplantation and development of hematopoietic chimerism or tolerance induction by intrathymic inoculation of alloantigen could effectively prevent chronic rejection in an established model of chronic rejection. Bone marrow chimeras were developed in F-344 hosts by transplantation of T cell-depleted allogeneic marrow (TCD A BMT). Another set of F-344 hosts was inoculated with intrathymic allogeneic bone marrow cells. Heart grafts in these animals demonstrated tolerance for 120 days after transplantation. Control F-344 animals treated with a short course of cyclosporine consistently developed chronic rejection by 120 days following heart transplantation. Strikingly absent from the tolerant animals was any sign of graft arteriosclerosis, which was demonstrated in the vast majority of control animals. Analysis of cytokine mRNA profiles at 30 days following heart transplantation demonstrated differences between control and tolerant animals. These results suggest that tolerance induction can effectively prevent chronic rejection.

Animals↗
PubMed1995

Treatment of systemic and renal-limited vasculitic disorders with pooled human intravenous immune globulin.

Idiopathic crescentic glomerulonephritis is characterized by an absence of immunohistological evidence of immune deposits, often with evidence of segmental glomerular necrosis. Such pauciimmune crescentic glomerulonephritis is the most common renal manifestation seen in patients with Wegener's granulomatosis, polyarteritis nodosa, and glomerulonephritis associated with other systemic vasculitic disorders (i.e., Churg-Strauss syndrome). Recently, the idiopathic crescentic glomerulonephritides, either in renal-limited form or in association with other systemic vasculitic disorders, were found to have in common a serologic marker, antineutrophil cytoplasmic autoantibodies. These cytoplasmic and perinuclear antineutrophil cytoplasmic autoantibodies are specific for constituents of neutrophil primary granules and monocyte lysosomes. As serologic markers for vasculitic disorders, they are also felt to be directly involved in the pathogenesis of necrotizing vascular injury. In vitro, both perinuclear and cytoplasmic antineutrophil cytoplasmic autoantibodies are capable of causing cytokine-primed neutrophils to undergo degranulation and respiratory burst, releasing toxic oxygen species and lytic enzymes. Anti-idiotype antibodies which inhibit antineutrophil cytoplasmic autoantibodies in vitro, in a V region-dependent manner, are found in pooled human gamma-globulin preparation. Intravenous immune globulin infusions in vivo have produced dramatic improvements in the necrotizing vascular injury produced by antineutrophil cytoplasmic autoantibodies, and a rapid reduction in these autoantibody levels is seen post-intravenous immune globulin infusion in most patients. The proposed mechanisms of action of intravenous immune globulin in vasculitic disorders include Fc-dependent mechanisms, and F(ab')2-dependent mechanisms are likely important. Intravenous immune globulin infusions appear to have an important place in the management of the necrotizing vascular injury. Blinded, randomized, placebo-controlled trials will be necessary to establish definitely intravenous immune globulin as a therapeutic option in vasculitic disorders.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1995

Cytokine gene expression in rejecting and tolerant rat lung allograft models: analysis by RT-PCR.

UNLABELLED: Cytokine gene expression is a critical component of the lung allograft rejection (AR) response and tolerance development in rat models. In order to determine the specificity of cytokine gene expression for AR and tolerance, we examined cytokine (interleukin-2) (IL-2), (gamma-interferon) (gamma-IFN), IL-4, IL-10 and tumor necrosis factor-alpha (TNF-alpha) and control (cyclophilin) mRNA levels in two models of rat lung allograft rejection by RT-PCR (reverse transcriptase polymerase chain reaction), Southern blotting. The first model (WKY-->F344) develops a mild to moderate lymphocytic infiltrate on days 14-21 post-transplant (stage II-III AR), which spontaneously resolves by day 35 post-transplant with subsequent development of allograft tolerance (grafts surviving without evidence of AR for > 140 days). Conversely, F344-->WKY develops a similar lymphocytic infiltrate by day 14 post-transplant, but by day 21 post-transplant the graft shows severe AR (stage III-IV) and has haemorrhagic infarction with alveolar haemorrhage. METHODS: RNA was extracted from allografts removed on days 3, 7, 14, 21, 35 and 42 post-transplant. Five animals for each group (WKY-->F344) and F344-->WKY) were examined at each time point, except that no animals in the F344-->WKY were examined on day 42. cDNA was synthesized from total extracted RNA and primers specific for rat TNF-alpha, rat IL-2, rat gamma-IFN, rat IL-4, rat-IL-10 and rat cyclophilin were used for gene-specific amplification. (TNF-alpha, gamma-IFN, IL-10, 20 cycles; IL-2, IL-4, 30 cycles; cyclophilin, 20 cycles). The cycles numbers chosen for comparison were found to be optimal during preliminary experiments and occurred during the exponential phase of amplification. PCR products were electrophoresed on a polyacrylamide gel and silver-stained. Gels were subsequently electrotransferred to nylon membranes which were probed with murine cDNAs specific for IL-2, gamma-IFN IL-4, IL-10 and TNF-gamma. RESULTS: Cyclophilin gene expression was similar for both models at all time points tested; this also served as an internal standard for RT-PCR. In the WKY-->F344 tolerance model, TNF-alpha mRNA levels were not detectable on days 3 and 7 post-transplant, were at very low levels on day 14 and were undetectable on day 21 post-transplant. In marked contrast, the F344-->WKY rejection model showed TNF-alpha mRNA present on day 3 which increased markedly on day 7 and peaked on day 14 post-transplant. TNF-alpha mRNA levels decreased on days 21 and 35 post-transplant, a time when the lung was undergoing AR. The pattern of IL-2 and gamma-IFN mRNA expression was similar to that for TNF-alpha. However, IL-2 mRNA was clearly detectable in the WKY-->F344 tolerance model on day 7 and gamma-IFN was not present until day 14 post-transplant. The F344-->WKY rejection model showed very high levels of IL-2 and gamma-IFN on day 3 which peaked on day 14. The ratio of IL-2/IL-10 in the F344-->WKY rejection model was more than 5 times that seen in the WKY-->F344 tolerance model on day 3 (p < 0.0005). The ratio of IL-2/IL-4 was higher (1.5 times) in the F344-->WKY rejection model than in the WKY-->F344 tolerance model (p < 0.007) on day 3. On day 14 post-transplant, the IL-2/IL-10 ratio in the F344-->WKY rejection model was three times that of the tolerance model (p < 0.0015). The IL-2/IL-4 ratio was 3.5 times greater in the WKY-->F344 tolerance model than in the rejectin model (p < 0.003). This was due to equal expression of IL-2 and IL-4 in the rejection model, but poor IL-4 expression in the tolerance model. CONCLUSIONS: 1) The WKY-->F344 tolerance model develops mild to moderate lymphocytic infiltrates on day 14 which is associated with low level IL-2, gamma-IFN and TNF-alpha gene expression. IL-10 and IL-4 are present at day 3; however, by day 14, IL-10 is the predominantly expressed Th2 cytokine and IL-4 is not expressed. The infiltrates ultimately resolve and the animals develop a functional tolerance to their grafts.4

Animals↗
PubMed1995

Alterations of the interleukin-4 pathway in production of tolerance by mixed hematopoietic chimerism.

BACKGROUND: The induction of specific tolerance could prevent acute and chronic rejection, as well as immunosuppressive complications, in recipients of vascularized organ allografts. Mixed hematopoietic chimerism is one approach to allogeneic tolerance. In these studies we examined whether mixed chimerism can confer tolerance to heart allografts across major and minor histocompatiblity barriers. We also examined the transcription of cytokine genes within the allografts of tolerance animals and in cell culture. METHODS: Adult Lewis rats were lethally irradiated and reconstituted with a mixture of 50 x 10(6) T-cell depleted bone marrow cells. Chimeric animals received heterotopic donor strain and third-party heart allografts and were assessed daily for rejection. Another set of chimeras received heart allografts that were examined at varying time points for transcription of cytokine genes by reverse-transcriptase polymerase chain reaction. RESULTS: Median graft survival in control animals was 6 days. Graft survival in 11 mixed chimeras ranged from more than 165 to more than 274 days (p < 0.001), and no episode of rejection or graft-versus-host disease was observed. Examination of cytokine transcriptions revealed dramatic alterations in interleukin-4 transcription in vivo and in vitro. CONCLUSIONS: Alterations in cytokine gene transcription are descriptive of tolerance in this model. Mixed chimerism confers long-term unresponsiveness to heart allografts across major and minor histocompatibility barriers with desirable features for clinical application.

Animals↗
PubMed1995

Immunologic monitoring of OKT3 induction therapy in cardiac allograft recipients.

OKT3 induction therapy was monitored in 31 cardiac allograft recipients during the 1st year posttransplant. Serum level of OKT3, anti-OKT3 antibodies, and interleukin-2 (IL-2) were monitored during the first 2 months posttransplant. These values were retrospectively correlated with allograft rejection episodes which occurred during the 1st year posttransplant and allograft survival rates over a 3-year observation period. We found that OKT3 induction therapy (10-14 days) was not associated with the development of anti-OKT3 antibodies manifest by dropping OKT3 levels during OKT3 therapy, and is not associated with the development of vascular rejection in our patient population. Patients with high titer ant-OKT3 antibodies, erratic serum OKT3 levels, and/or high serum IL-2 levels (> or = 5 ng/ml) during the first 2 months posttransplant showed a higher incidence of allograft rejection (predominantly cellular rejection) during the 1st year posttransplant and showed lower allograft survival rates. We also showed that a concomitant elevation of serum IL-2 levels was found in patients who developed anti-OKT3 antibodies. CD3+ T-cell levels were not predictive of inefficacy of OKT3 therapy. We conclude that immunologic monitoring of serum OKT3, anti-OKT3 antibody, and possibly serum IL-2 levels is critical for identification of patients who develop early, OKT3-resistant rejection episodes and for the identification of patients who may be more susceptible to allograft rejection and decreased allograft survival long after completion of OKT3 therapy.

Antibodies, Anti-Idiotypic↗
PubMed1994

Gamma-interferon gene expression in human renal allograft fine-needle aspirates.

Cytokines appear to play a major role in acute transplant rejection (AR); however, the specific cytokines initiating AR are not known. To investigate gamma-interferon messenger RNA (mRNA) as a key factor in AR induction, we performed reverse transcription-polymerase chain reaction (RT-PCR) on renal allograft fine-needle aspirates (FNA). Fifteen FNA from 15 patients were processed and interpreted in the standard fashion, the percent of tubular cells with MHC class II expression (DR) quantitated, and aliquots of FNA obtained for RT-PCR. RT-PCR was performed with primers to gamma-IFN with cyclophylin and insulin primers as controls. Retrospective clinical diagnoses were made for each FNA sample. Following RT-PCR, all FNA and FNAs from control normal and AR nephrectomy specimens had cyclophylin present, and in the 9 samples tested insulin was absent. Five patients had AR clinically and by FNA criteria; all 5 had elevated DR and gamma-IFN mRNA present in FNA. Five patients had tubular necrosis or cyclosporine toxicity clinically, and FNA without immune activation or elevated DR and negative gamma-IFN mRNA. Two patients had immune activation by FNA with elevated DR; both FNA expressed gamma-IFN mRNA by Southern blot, one only weakly, and both patients subsequently developed clinical AR. Two patients had recently treated AR, one with persistent DR elevation without-immune activation and negative gamma-IFN mRNA in FNAs. This study demonstrates that RT-PCR can be performed with renal allograft FNA samples. The findings suggest intragraft gamma-IFN mRNA expression occurs in active AR preceding clinical AR, thus defining incipient AR. Detection of gamma-IFN mRNA may offer an early diagnostic tool for detection of AR.

Base Sequence↗
PubMed1994

Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ.

Patients awaiting solid organ transplantation who are highly sensitized to HLA antigens remain problematic in terms of finding compatible (crossmatch-negative) donors. We have used intravenous gammaglobulin (IVIG; 10% Gamimune N) to determine both its efficacy in reducing panel-reactive antibodies in vitro and the prognostic value of the in vitro testing for in vivo efficacy. In 18 patients with PRAs ranging from 40 to 100% (mean: 77%) we found a reduction in absolute PRA of 4-70% (mean decrease: 35%; percent inhibition: 4-100%; residual PRA 0-96%). In 7 cases, the residual antibody specificity could be easily determined and often appeared to include a short HLA-A2. This was independent of A2 subtype as determined by PCR-SSOP. Testing the IVIG on a panel of 21 HLA reagent alloantisera resulted in heterogeneous inhibitory patterns (7 complete, 3 partial, 8 differential, 3 none) independent of titer or specificity. In vivo administration to a 13-year-old kidney patient awaiting retransplant resulted in a PRA drop from 95% to 15% and successful retransplantation (now 11 months post-transplant). More impressively, successive in vivo administration of IVIG to a sensitized (anti-HLA-A2, A68, A69; B57, B58) heart transplant candidate resulted in successful transplantation with an A2+ histoincompatible heart. The patient experienced only one subclinical humoral rejection in the first 5 months posttransplant. Biochemical studies to determine the effective component of IVIG show that it is the IgG fraction and not soluble antigen or the minor IgM or IgA contaminants that is responsible. This suggests an antiidiotypic modulation of anti-HLA antibodies in vitro and in vivo.

HLA Antigens↗
PubMed1994

Modulation of immunoglobulin production and cytokine mRNA expression in peripheral blood mononuclear cells by intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) has the potential to regulate Ig production, but the mechanism(s) responsible for this effect is unknown. In experiments reported here, we examined the ability of IVIG to regulate Ig production in human peripheral blood mononuclear cells (PBMCs) stimulated with pokeweed mitogen (PWM). IVIG (2-10 mg/ml) showed a potent (80-85%) inhibition of PWM-stimulated IgG, IgM, and IgA production. To determine more precisely how IVIG mediated the inhibition of Ig production, we studied Ig promoting cytokine gene expression after PWM stimulation with or without IVIG (2 and 10 mg/ml) using dot-blot techniques. RNA was isolated from PBMCs at predetermined time points and probed with cDNAs specific for human cytokines (IL-1 beta, IL-2, IL-2R, IL-4, IL-5, IL-6, gamma-IFN, and TNF-alpha). IL-6 mRNA accumulation was maximal at 4.5 hr post-PWM stimulation and was inhibited 64-75% when IVIG (10 mg/ml) was present. gamma-IFN mRNA levels peaked at 72 hr poststimulation and were also 68-75% inhibited by IVIG. IL-2 mRNA levels peaked at 4.5 hr and were 23-46% inhibited by IVIG. The inhibitory effect of IVIG on production of these cytokines (IL-6 and gamma-IFN) was also observed at the protein level in sonicated PBMCs after incubation with PWM and IVIG. The mRNA levels for other cytokines were not or only minimally inhibited by IVIG. Addition of IL-6, gamma-IFN, or IL-2 partially restored Ig production in IVIG-treated PWM-stimulated cultures, suggesting that inhibition of other cytokines or another mechanism(s) independent of cytokine inhibition might also be involved, although inhibition of IL-6, gamma-IFN, and IL-2 may be one of the critical factors in the suppression of Ig production by IVIG.

Cells, Cultured↗
PubMed1994

Treatment of autoimmune diseases and systemic vasculitis with pooled human intravenous immune globulin.

Treatment of autoimmune and vasculitic disorders with intravenous immune globulin (IVIG) has shown great promise. IVIG appears to provide large amounts of immunoregulatory substances that have the capacity to regulate the immune system in various ways. The ability of IVIG to regulate deleterious autoimmune responses and disease is largely directly related to its ability to stimulate the production of anti-idiotypic autoantibodies after infusion. In this respect, IVIG represents a novel immunoregulatory agent with the ability to control autoimmune and vasculitic disorders without subsequent predisposition to infectious complications. Future work and controlled clinical trials will be necessary to prove the efficacy of this therapy for specific autoimmune and vasculitic disorders.

Antibodies, Anti-Idiotypic↗