Studies of natural killer cell activity in a drug-free, healthy population. Response to a challenge with taxol, estramustine and lipopolysaccharide.
Preincubation of peripheral blood lymphocytes with the microtubule disturbing agents estramustine (ETMN; n = 7, final conc. 20 microM) or taxol (TX; n = 13, final conc. 10 microM), resulted in a statistically significant inhibition of natural killer cell activity [(NKCA); baseline (x +/- SD; expressed as percentage of specific chromium release) of 32.2 +/- 30.5 and 34.4 +/- 27.7 and drug treated samples of 13.9 +/- 19.9 and 12.5 +/- 20.8, respectively; Student's paired t-test p < 0.005]. Furthermore, most individual values for NKCA in the drug preincubated samples were at least 20% below the same subject baseline lytic function (except for TX sample No.1), and NKCA was non detectable in 4 out of 7 and 5 out of 13 samples (pretreatment with either ETMN or TX< respectively). The use of other concentrations and different preincubation times for these chemotherapeutic agents also produced NKCA inhibition, which was time and dose dependent. Preincubation with lipopolysaccharide (LPS; n = 16, final conc. 50 micrograms/ml), an endotoxin prominently involved in the etiology of septic shock, resulted in a statistically significant enhancement of NKCA [baseline (x +/- SD; expressed as percentage of specific chromium release) of 25.4 +/- 20.4 and LPS treated sample of 36.6 +/- 17.4, respectively; Student's t paired t-test p < 0.005]. At least a 20% increase in NKC lytic function over its own baseline value was recorded for each and everyone of the samples tested with LPS.2+ the pathophysiology associated with septic shock.
Puente
J
J
Department of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, Santiago, Chile.
Diaz
M
M
Salas
M A
MA
Miranda
D
D
Gaggero
A
A
Wolf
M E
ME
Mosnaim
A D
AD
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004961:Estramustine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000494:pharmacology*; D016037:Single-Blind Method; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D004961:Estramustine; D017239:Paclitaxel