Peripheral Leukocyte Concentrations Research Articles

Photoperiod- and Triiodothyronine-dependent Regulation of Reproductive Neuropeptides, Proinflammatory Cytokines, and Peripheral Physiology in Siberian Hamsters (Phodopus sungorus).

Seasonal trade-offs in reproduction and immunity are ubiquitous in nature. The mechanisms that govern transitions across seasonal physiological states appear to involve reciprocal switches in the local synthesis of thyroid hormone. In long-day (LD) summer-like conditions, increased hypothalamic triiodothyronine (T3) stimulates gonadal development. Alternatively, short-day (SD) winter-like conditions increase peripheral leukocytes and enhance multiple aspects of immune function. These data indicate that the localized effects of T3 in the hypothalamus and leukocytes are photoperiod dependent. We tested the hypothesis that increased peripheral T3 in SD conditions would increase aspects of reproductive physiology and inhibit immune function, whereas T3 injections in LD conditions would facilitate aspects of immune function (i.e., leukocytes). In addition, we also examined whether T3 regulates hypothalamic neuropeptide expression as well as hypothalamic and splenic proinflammatory cytokine expression. Adult male Siberian hamsters were maintained in LD (15L:9D) or transferred to SD (9L:15D) for 8 weeks. A subset of LD and SD hamsters was treated daily with 5 µg T3 for 2 weeks. LD and SD controls were injected with saline. Daily T3 administration in SD hamsters (SD+T3) resulted in a rapid and substantial decrease in peripheral leukocyte concentrations and stimulated gonadal development. T3 treatment in LD (LD+T3) had no effect on testicular volumes but significantly increased leukocyte concentrations. Molecular analyses revealed that T3 stimulated interleukin 1β messenger RNA (mRNA) expression in the spleen and inhibited RFamide Related Peptide-3 mRNA expression in the hypothalamus. Moreover, there was a photoperiod-dependent decrease in splenic tumor necrosis factor-α mRNA expression. These findings reveal that T3 has tissue-specific and photoperiod-dependent regulation of seasonal rhythms in reproduction and immune function.

Melatonin acts at the suprachiasmatic nucleus to attenuate behavioral symptoms of infection.

In common with reproduction, immune function exhibits strong seasonal patterns, which are driven by annual changes in day length (photoperiod) and melatonin secretion. Whereas changes in melatonin communicate seasonal time into the reproductive axis via subcortical receptors, the relevant melatonin targets for communicating seasonal time into the immune system remain unspecified. The authors report that melatonin implants targeting the hypothalamic suprachiasmatic nuclei (SCN) induced a winter phenotype in the immune system. SCN melatonin implants attenuated infection-induced anorexia and cachexia, indicating that the SCN mediate the effects of melatonin on these behavioral and metabolic symptoms of infection. However, SCN melatonin implants failed to induce winter-like peripheral leukocyte concentrations or behavioral thermoregulatory responses to infection. In contrast, subcutaneous melatonin implants induced winter-like changes in all behavioral and immunological parameters. Melatonin acts directly at the SCN to induce seasonal changes in neural-immune systems that regulate behavior. The data identify anatomical overlap between neural substrates mediating the effects of melatonin on the reproductive and immune systems but also suggest that the SCN are not the sole mediator of photoperiodic effects of melatonin on immunity.

The response of leukocyte subsets and plasma hormones to interval exercise

Aerobic exercise has an established role in modulation of peripheral leukocyte concentrations. However, the effects of intense interval exercise, as employed by athletes in a range of sports, has been given little attention. Eight trained male athletes of mean age (SD) = 31.5 (4.5) yr; VO2max = 64.3 (3.8) ml.kg-1.min-1 undertook an intense interval exercise protocol (treadmill running) to exhaustion. Subjects completed an average of 15.6 1-min efforts. The protocol produced a biphasic leukocytosis: an initial (immediately posttest) leukocytosis resulting from mobilization of lymphocytes (CD3+, CD4+, CD8+, CD16+/56+, CD3+HLA/DR+) (all P < 0.01), with the later (6 h) leukocytosis resulting from mobilization of granulocytes and monocytes (both P < 0.01). This protocol modified significantly the peripheral blood concentration of the hormones cortisol (both total and free), norepinephrine, DHPG, and dopamine (all P < 0.01). Modulation of peripheral leukocyte subsets induced by interval exercise correlated with both the number of exercise efforts performed and the concomitant changes in peripheral hormone concentrations. Sustained alterations in plasma catecholamine levels in the posttest period may have important metabolic and immunological implications for athletes undertaking regular interval training.

Bone Marrow Myelopoiesis in Rats After 10%, 20%, or 30% Thermal Injury

The high incidence of serious opportunistic infections that follow thermal injuries is well documented. Normal levels of functioning leukocytes are essential to the host's ability to resist infection. This study examined alterations in murine granulopoiesis after the inducement of a standardized, sublethal, third-degree burn covering 10%, 20%, or 30% of the dorsal body surface area. Significant alterations arose in peripheral leukocyte concentrations after inducement of uncomplicated thermal injury. In general, within the first day of injury, all three trauma levels produced a peripheral leukocytosis that lasted for 35 days or more. The leukocytoses that followed 20% and 30% injuries were similar and in numerous respects paralleled previously reported human peripheral responses after similar levels of thermal trauma. Differential examinations of peripheral blood demonstrated the peripheral leukocytosis to be due primarily to the influx of morphologically mature-appearing polymorphonuclear neutrophils. Premature bone marrow release did not appear to be a factor as immature polymorphonuclear neutrophils were seldom greater than 2% of polymorphonuclear neutrophil totals. Bone marrow granulopoietic activity was examined by in vitro clonal cell culture techniques and assessed over a period of 35 days after injury. Granulocyte-macrophage colony forming cells (GM-CFC), indicative of marrow progenitor cell concentrations, were significantly increased for 28 to 35 days after 10% injury and 11 to 14 days after 20% or 30% injury. Normal or increased progenitor cell concentrations and a lack of morphologically appearing premature forms suggest that the leukocytosis is the result of injury-induced alteration(s) in polymorphonuclear neutrophil margination or release mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

STUDIES ON NORMAL AND IMMUNE LYMPHOCYTE TRANSFER REACTIONS IN GUINEA PIGS, WITH SPECIAL REFERENCE TO THE CELLULAR CONTRIBUTION OF THE HOST

Using guinea pigs of strains 2 and 13 and their F(1) hybrids as experimental subjects, various lines of evidence have been obtained that in this species, as in all others tested, the only significant cellular antigens with which donor lymphocytes engage when normal and immune lymphocyte reactions are incited are radiosensitive leukocytes. Constitutive cells of the skin are unimportant. (a) The intensities of these reactions in irradiated subjects are dependent upon the peripheral leukocyte concentration. When this falls below a certain threshold no reactions are incitable. (b) Highly leukopenic animals are capable of developing immune lymphocyte transfer (ILT) reactions if normal lymphoid cells of their own genetic constitution are mixed with the putative attacking donor cells, as "supplementing antigen," before inoculation. (c) Radiation-chimeric strain 13 animals having F(1) hybrid leukocytes in their bloodstream give typical ILT reactions when challenged intradermally with strain 13 anti-2 node cells. Exposure of strain 2 animals to 600 R does not prevent their becoming actively immunized if, 24 hr later, they are injected intradermally with strain 13 lymphocytes. However, this sensitization, revealed by the host's capacity to give delayed hypersensitivity reactions, wanes as leukopenia progresses. On the basis of this and other findings it is argued that the flare-up stage of the NLT reaction in preirradiated hosts is mainly an expression of host sensitivity against the transferred alien cells. Two unexpected observations have been made in the course of this study: (a) F(1) hybrid animals developed what appeared to be a strong delayed hypersensitivity after intradermal inoculation with parental strain lymphoid cells or antigenic extracts prepared from them. (b) If strain 13 guinea pigs which had been sensitized against strain 2 tissue antigens by intradermal injection of lymphocytes 7 days beforehand were inoculated intravenously with strain 2 antigenic extract a significant proportion of the animals developed severe delayed necrotizing reactions, recall flares, at some or all of the healed skin inoculation sites.

Leukapheresis in Man. III. Hematologic Observations in Patients with Leukemia and Myeloid Metaplasia

Abstract Eleven patients with leukemia and one patient with myeloid metaplasia underwent leukapheresis on 18 occasions for 94 to 275 minutes during which 93 to 1668 x 109 leukocytes were removed. All patients exhibited a significant and continued decline of peripheral leukocyte concentration during or after the procedure. In 12 of the 18 instances, the leukocyte concentration returned slowly to the initial leukocyte level within 1 hour to 22 days. The number of leukocytes withdrawn represented 16 to 247 per cent of the initial circulating volume removed at a rate of 0.13 to 1.14 leukocyte blood volumes per hour. The RAR was 1:1 to 12:1 to the circulating leukocyte number. Rate of replenishment of the circulating immature leukocyte numbers were 4.0 x 107 to 52.2 x 109/Kg./day. The PMN’s were replaced at rates of 10 x 106 to 7.05 x 109/Kg./day which were equal to or slower than in normal subjects. Changes in number occurred in the dominant leukemic cell types without significant shifts in the differential counts. No changes in marrow population other than a slight decrease in cellularity were observed. The data indicate that in the leukemic patient the peripheral leukocyte concentration was not maintained or replenished promptly following the withdrawal of sizeable quantities of leukocytes, demonstrating a block in transfer of leukocytes from the tissues to the blood. This is in marked contrast to the leukocytosis and marrow stimulation observed in hematopoietically normal subjects following leukaphereses. The platelet counts fell promptly during leukapheresis, returning toward control levels in eight studies within 7 hours following the procedure. In four studies the platelet counts returned to control levels in 3 to 9 days. The changes in platelet concentrations were similar to those observed with hematologically normal subjects. The size of the platelet reservoir in these leukemic patients is about twice that of the circulating blood.