Sisson M E, Rieder M J, Bird I A, Almawi W Y
Department of Paediatrics, J.P. Robarts/Child Health Research Institutes, Children's Hospital of Western Ontario, University of Western Ontario, London, Canada.
Int J Immunopharmacol. 1997 May;19(5):299-304. doi: 10.1016/s0192-0561(97)00027-1.
To determine the effect(s) of reactive sulfonamide metabolites on antibody production by human lymphocytes.
Human peripheral blood cells (PBMCs) were isolated from control volunteers and incubated with the hydroxylamine of sulfamethoxazole (SMX H/A), a reactive metabolite of the most commonly used sulfonamide, in increasing concentrations. PBMCs were then stimulated to produce antibody with pokeweed mitogen. After incubation for 8 days, concentrations of IgG and IgM were determined in supernatant using an ELISA assay.
Production of both IgG and IgM was significantly suppressed by sub-lethal concentrations of SMX H/A in a concentration-dependent fashion (p < 0.05). Suppression was more marked for IgM production (maximal decline to 80% of baseline antibody production) than for IgG production (maximal decline to 57% of baseline antibody production). No suppression was seen when cells were incubated with sulfamethoxazole in concentrations up to 400 microM. This suppression was not related to changes in cell viability; at a concentration of 25 microM of SMX H/A, IgM and IgG concentration were reduced by 47 +/- 8.7% and 73 +/- 7.2%, while cell viability (percentage of live cells) was 93 +/- 5%. Suppression was time-dependent, increasing over the incubation periods to reach a plateau after 2 h of incubation.
Sulfonamide reactive metabolites, in concentrations which are achieved during therapy, suppress antibody production by PWM-stimulated human cells. This may explain, in part, the alterations in immunity associated with hypersensitivity reactions to the sulfonamides. This may also have implications for patients receiving sulfonamide therapy and concurrent immunosuppressive therapy.
确定反应性磺胺代谢产物对人淋巴细胞抗体产生的影响。
从对照志愿者中分离出人外周血单个核细胞（PBMC），并与最常用磺胺的反应性代谢产物磺胺甲恶唑羟胺（SMX H/A）以递增浓度孵育。然后用商陆有丝分裂原刺激PBMC产生抗体。孵育8天后，使用酶联免疫吸附测定法测定上清液中IgG和IgM的浓度。
亚致死浓度的SMX H/A以浓度依赖性方式显著抑制IgG和IgM的产生（p < 0.05）。对IgM产生的抑制比对IgG产生的抑制更明显（最大下降至基线抗体产生的80%）（IgG最大下降至基线抗体产生的57%）。当细胞与浓度高达400微摩尔的磺胺甲恶唑孵育时，未观察到抑制作用。这种抑制与细胞活力的变化无关；在25微摩尔的SMX H/A浓度下，IgM和IgG浓度分别降低了47±8.7%和73±7.2%，而细胞活力（活细胞百分比）为93±5%。抑制作用具有时间依赖性，在孵育过程中增加，孵育2小时后达到平台期。
在治疗过程中达到的浓度下，磺胺反应性代谢产物抑制经PWM刺激的人细胞的抗体产生。这可能部分解释了与磺胺类药物超敏反应相关的免疫改变。这也可能对接受磺胺类药物治疗和同时进行免疫抑制治疗的患者产生影响。
