{'fraction_non_alphanumeric': 0.03280839895013123, 'fraction_numerical': 0.01115485564304462, 'mean_word_length': 5.963470319634703, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Nordihydroguaiaretic Acid Blocks IL‐2‐Independent Lymphocyte Proliferation and Enhances Responses to PPD

The authors examined the mechanism by which the non‐specific lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) inhibits human lymphocyte proliferative responses and compared its effects with those of cyclosporine (CsA). It was found that CsA‐resistant proliferative responses induced by direct PK‐C activators such as mitogenic concentrations of the phorbol ester TPA or the putative anti‐tumour agent bryostatin 1 (bryo 1) were inhibited in a concentration‐dependent manner by NDGA (IC50 = 2 μM). In contrast, CsA‐sensitive IL‐2‐dependent proliferative responses induced by PHA, anti‐CD3 or the purified protein derivative (PPD) of M. tuberculosis were not significantly inhibited by NDGA concentrations as high as 8 μM. The expression of the IL‐2R by lymphocytes was also resistant to NDGA concentrations that effectively blocked the mitogenic effects of TPA or bryostatin, but could be inhibited by higher concentrations of NDGA (IC50 = 8 μM). In addition, NDGA, but not CsA, blocked the production of IL‐6 by human mononuclear cells. Furthermore, PPD‐induced proliferation was significantly enhanced by NDGA. These data would suggest that NDGA at concentrations below 8 μM selectively inhibits IL‐2‐independent proliferation. NDGA’s ability to inhibit IL‐6 while enhancing the proliferative response to PPD may indicate an anti‐inflammatory therapeutic potential of anti‐oxidants in mycobacterial infections.