In defining host resistance factors in
uremia, experiments were designed to assess the effect of
renal failure serum upon the reactivity of normal human lymphocytes to
phytohemagglutinin in vitro. Normal buffy coat cells were resuspended in sera obtained from normal subjects and from 14 patients with
renal failure, then stimulated with
phytohemagglutinin M and the cellular response measured by the increase in
thymidine or
uridine uptake. The mean
thymidine uptake by stimulated cells in normal sera was 14,389 +/-1695 (SEM) cpm per 2 x 10(6) lymphocytes.
Uridine uptake under the same conditions was 12,540 +/-1887 cpm. Compared to these are a mean
thymidine uptake of 2740 +/-457 cpm and
uridine uptake of 3928 +/-667 cpm in
renal failure sera. Both differences are significant at P<0.01 level. For controls representing "
chronic illnesses," sera from patients with
pneumococcal meningitis,
cirrhosis of the liver without
jaundice,
rheumatoid arthritis, and
paraplegia with
urinary tract infection did not cause suppression. No single
drug had been taken by all the
renal failure patients; three patients were taking no drugs. The serum from one patient with
acute renal failure suppressed
thymidine uptake while her serum obtained after recovery from her illness supported a normal lymphocyte response. Improvement of lymphocyte response was also noted in 9 of 10 sera obtained from patients immediately after
hemodialysis. These observations plus the inhibition of stimulated cells by normal serum mixed with
renal failure serum indicate the presence of a dialyzable inhibitory factor rather than the absence of a supporting factor in the
renal failure sera. Lymphocytes preincubated for 24 hr in
renal failure serum responded normally when transferred to normal serum and stimulated. Cells stimulated in normal serum and transferred to
renal failure serum within the initial 24 hr of incubation demonstrated depressed
thymidine uptake. Also, cell survival for 72 hr incubation as judged by
trypan blue exclusion and
chromium-51 release was similar in normal and
renal failure sera. Thus, the suppressive effect of
renal failure serum does not depend upon the initial
phytohemagglutinin-cell interaction nor upon a significant cytotoxic effect. These studies demonstrate that a dialyzable factor(s) in the serum of patients with
renal failure can greatly suppress one parameter by which an immune function of circulating lymphocytes is assessed and provides at least, a partial explanation for delayed homograft rejections in
renal failure as well as the susceptibility of such patients to various
infections.