Klingemann H G, Tsoi M S, Storb R
Blood. 1986 Jul;68(1):102-7.
Prostaglandins are said to influence T and B cell function by inhibiting the generation of interleukin 2 (IL 2) and the formation of suppressor lymphocytes. After bone marrow transplantation, patients usually have a profound immunodeficiency that persists in recipients with chronic graft-v-host disease (GVHD) and generally resolves in long-term survivors without GVHD. In vitro tests of lymphocyte function such as allogeneic mixed lymphocyte culture (MLC) and cell-mediated lympholysis (CML) have been shown to be impaired in many patients. We postulated that prostaglandin E2 (PGE2) plays a role in the impaired in vitro tests. To test this hypothesis, we studied in vitro tests in the presence of PGE2 antagonists, indomethacin, and anti-PGE2 antiserum with cells from 22 short-term patients (less than 100 days postgrafting) and 32 long-term survivors with or without GVHD. Results show that blockade of PGE2 release by indomethacin and anti-PGE2 significantly (P less than .01) enhanced the MLC (+67%) and the CML responses (+10.5%) of cells from long-term survivors with chronic GVHD but not from those of long-term, stable recipients. No enhancement of MLC and CML activity was observed with cells from donors of long-term recipients. In patients shortly after marrow grafting, enhancement in the MLC was not significant. However, CML activity in this patient group was significantly increased (+12.5% in recipients with no GVHD, 8.5% in those with acute GVHD, P less than .01). Indomethacin also suppressed the activity of nonspecific suppressor cells in patients with chronic GVHD. When cells from patients with chronic GVHD were treated with recombinant IL 2 and IL 2 combined with indomethacin, it was possible to get an additional augmentation of lymphocyte proliferation after the addition of indomethacin to IL 2-treated cultures. Thus it is very likely that PGE2 inhibits T lymphocyte proliferation, not exclusively by inhibition of IL2 production or activity. We conclude that PGE2, among other factors, may play a role in the pathogenesis of the immunodeficiency after transplantation. PGE2 does not act primarily by interfering with IL2 but presumably by inducing a suppressorlike activity.
据说前列腺素通过抑制白细胞介素2（IL - 2）的产生和抑制性淋巴细胞的形成来影响T细胞和B细胞的功能。骨髓移植后，患者通常会出现严重的免疫缺陷，这种缺陷在患有慢性移植物抗宿主病（GVHD）的受者中持续存在，而在没有GVHD的长期存活者中通常会消退。淋巴细胞功能的体外试验，如异体混合淋巴细胞培养（MLC）和细胞介导的淋巴细胞溶解（CML），已被证明在许多患者中受损。我们推测前列腺素E2（PGE2）在体外试验受损中起作用。为了验证这一假设，我们用PGE2拮抗剂、吲哚美辛和抗PGE2抗血清对22名短期患者（移植后不到100天）以及32名有或没有GVHD的长期存活者的细胞进行了体外试验研究。结果表明，吲哚美辛和抗PGE2对PGE2释放的阻断显著（P < 0.01）增强了患有慢性GVHD的长期存活者细胞的MLC（+67%）和CML反应（+10.5%），但长期稳定的受者细胞则没有增强。长期受者供体的细胞未观察到MLC和CML活性增强。在骨髓移植后不久的患者中，MLC的增强不显著。然而，该患者组的CML活性显著增加（无GVHD的受者中增加12.5%，急性GVHD的受者中增加8.5%，P < 0.01）。吲哚美辛还抑制了慢性GVHD患者中非特异性抑制细胞的活性。当用重组IL - 2以及IL - 2与吲哚美辛联合处理慢性GVHD患者的细胞时，在IL - 2处理的培养物中加入吲哚美辛后，有可能进一步增强淋巴细胞增殖。因此，很可能PGE2抑制T淋巴细胞增殖，并非仅仅通过抑制IL - 2的产生或活性。我们得出结论，PGE2以及其他因素可能在移植后免疫缺陷的发病机制中起作用。PGE2主要不是通过干扰IL - 2起作用，而是可能通过诱导一种类似抑制的活性起作用。
