Military Strategies for Sustainment of Nutrition and Immune Function in the Field (1999) / Chapter Skim
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20 Chronobiology of the Immune System
20 Chronobiology of the Immune System
Pages 437-496
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From page 437... ...
The inheritance of rhythm characteristics and genes and gene products determining the occurrence, the extent, and Me timing of the rhythmic variations have been described (Feldmann, 1 985; Konopka, 1 979; Lakatua, 1 994; Lee et al., 1 996; Myers et al., 1996; Peleg et al., 1989; Reinberg et al., 1985; Rensing, 1997, Young, 1993; Young et al., 1985~. Biologic rhythms of various frequencies were found in single cells and in cell organ cultures removed from the organism and studied in vitro (Edmunds, 1994; Milos et al., 1990; Morse et al., 1989; Schweiger et al., 1986~.
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From page 438... ...
Death or survival can be made experimentally a function of the time when the agent is injected. The development of an immune response involves a series of interactions between lymphocytes and other mononuclear cells that may include cell-to-cell communication; generation of immunoreactive molecules; immunoglobulin synthesis and secretion; expression of cell surface markers that are not generally found on resting cells or changes in their receptor density and activity; and finally cell proliferation of immunocompetent cells.
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From page 439... ...
Rhythmic variations in several frequencies are found in every step of the development of an immune response in the humoral as well as the cellular arm of the immune system. Rhythmic variations of the immune response in its different aspects have been studied most extensively in the circadian frequency range.
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From page 440... ...
It is of interest that there appear to be phase differences between different lymphatic organs and the bone marrow. Other evidence about the endogenous nature of circannual variations is the observation of freerunning circannual rhythms of body functions in human subjects (Haus and Touitou, 1994a)
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From page 441... ...
(1997~. BIOLOGIC RHYTHMS IN THE NUMBER AND FUNCTION OF CIRCULATING WHITE BLOOD CELLS The numbers of circulating white blood cells involved in the defense of the human body show high-amplitude circadian variations.
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. Figure 20-3 shows the circadian rhythms of the circulating white blood cells and platelets in 150 clinically healthy young adults (24 ~ 10 years of age)
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aIld Platelets (87 subjects) over a 24-h Span in Clinically Healthy Subjects Peak-Trough Difference (cells/mm3)
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From page 444... ...
In clinically healthy subjects, the circadian rhythm in the number of circulating lymphocytes is a very regular and highly reproducible phenomenon. The peak values occur in most diurnally active human subjects during the night 5000 4000 3000 2000 Lymphocytes 4750 4071 1 3672 3412 5370 1292 1644 1815 1798 4165 1270 12:00 16:00 20:00 00:00 04:00 08:00 Time (Clock Hour)
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air\ 2 00 18 00 00 00 06 00 Time (Clock Hour) FIGURE 20-5 Circadian variation in lymphocyte subtypes in 10 clinically healthy subjects.
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From page 446... ...
Mixed lymphocyte reactions (MLRs) In PHA-activated T-cells and autologous non-T-cell activation showed statistically significant circadian variations with proliferation response of T-cells in both types of autologous MLRs, but with an apparent phase difference between them.
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From page 447... ...
followed that of the circulating lymphocytes in the same clinically healthy subjects by about 2 hours (Levi et al., 1988a)
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FIGURE 20-9 Circadian variation in serum neopterin concentration in 29 patients with rheumatoid arthritis. SOURCE: Adapted from Suteanu et al.
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From page 449... ...
. The NK cell activity in the peripheral blood of clinically healthy adult subjects shows a reproducible circadian rhythm, with the activity being high in the early morning and declining to a minimum during the night hours (Abo et al., 1981; Angeli et al., 1992; Gatti et al., 1986, 1988; Moldofsky et al., 1986, 1989; Williams, et al.
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From page 450... ...
Circannual variations in the relative number of circulating T- and B-lymphocytes as determined by a bacterial adhesion test were described in clinically healthy human subjects, with the peak of the T-cells in late fall and of the B-cells in winter. The circannual variation was apparent in the subtypes only; the total number of lymphocytes in this study showed no statistically significant circannual variation (Bratescu and Teodorescu, 1981~.
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From page 451... ...
may in some subjects require several weeks to adapt the timing of the circadian rhythms in plasma cortisol and in circulating lymphocytes to the changed light-dark and activity-rest schedule serving as environmental synchronizer (Haus and Touitou, 1994 a,b; Reinberg and Sindensky, 1994~. A full-phase adaptation to the shift schedule may not occur at all in nonpermanent shift workers or in permanent shift workers if the subjects do not fully change their living habits during the week and return to a diurnal activity pattern on weekends (Haus et al., 1984~.
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From page 452... ...
BIOLOGIC RHYTHMS IN CYTOKINES AND THEIR INHIBITORS The central nervous system (CNS) , endocrine, and immune systems respond to physiological and pharmacological stimuli in a coordinated manner with bidirectional communication between the systems (Beneviste, 1992; Blalock, 1992, 1994; Rivier and Rivest, 1993; Smith, 1992~.
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From page 453... ...
A circadian rhythm in IL-1 concentration was found in the serum of clinically healthy subjects (Bourin et al., 1990~. Cytokines, including IL-1,B and tumor necrosis factor (TNF)
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From page 454... ...
and the response to challenge of the immunized organism after reintroduction of the antigen show circadian periodic variations in human subjects and in animals (Cove-Smith et al., 1978; Fernandes et al., 1976, 1977, 1980; Lee et al., 1977; Pownall et al., 1979~. In animal experiments, the instensity of the humoral immune response to T-cell-dependent and independent antigens shows circadian periodicity (Fernandes et al., 1974, 1976; Pownall and Knapp, 1980~.
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From page 455... ...
In patients with allergic rhinitis, circadian rhythms were detected in all three ~mmunoglobulins with a 3-h delay in the peaks of IgG and IgM as compared with healthy subjects (Cricchio et al., 1979) (Figure 20-10~.
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From page 456... ...
, and others (for review, see Levi and Halberg, 1982~. Seasonal variations or circannual rhythms in serum immunoglobulins were reported in clinically healthy subjects with peak levels of IgG, IgA, and IgM occurring during midsummer to midautumn (Lu et al., 1979; Reinberg et al., 1979~.
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From page 457... ...
Thus, both the disappearance of the virus particles from the circulating white blood cells and the disturbance of amino acid circadian periodicity occurred later after inoculation at 20:00 as compared with the inoculation at 8:00 A.M. These observations suggest that the effect of an infectious microorganism on the human host may depend to some degree on the time of exposure (Feigin et al., 1967a)
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From page 458... ...
Data thus far available on the response of human subjects to vaccination support the following conclusions: · Differences in immune response as a function of the circadian time of the introduction of antigen may occur as indicated by differences in antibody titer in clinically healthy subjects. These differences may be limited to certain antigens and/or to a certain degree of immune response and may also depend on other factors (such as seasonal variations)
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From page 459... ...
Clinically healthy, diurnally active human subjects testing positive for PPD (due largely to BCG3 vaccination) showed, when injected intradermally with PPD during different circadian stages, a circadian variation in response with a maximum at 07:00 and a minimum at 22:00.
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From page 460... ...
A similarity of timing of duration of circadian rhythms in diurnally active humans and nocturnal rodents is found also in the circadian rhythm of melatonin and of some red cell parameters in the peripheral blood (Haus et al., 1983~. TIME-DEPENDENT CHANGES IN CUTANEOUS ALLERGY AND ALLERGIC ASTHMA The cutaneous response to histamine and to the antigens of ragweed, grass pollen antigen, and house dust, varies in a circadian rhythmic fashion.
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From page 461... ...
(1987) found a fivefold greater mean concentration of IgE in asthmatics than in clinically healthy children, with a high-amplitude circadian rhythm equal to 30 percent of the 24-h mean in asthmatics, which was absent in the healthy subjects (Figure 20-11~.
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FIGURE 20-11 Circadian rhythm in serum immunoglobulin E (IgE) in children with allergic asthma is not evident in clinically healthy subjects.
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From page 463... ...
Interferon-a Tumor necrosis factor Factor S Muramyl peptides Vasoactive intestinal peptide Delta sleep-inducing peptide Krueger, 1990 Krueger, 1990 Krueger, 1990 Krueger, 1990 Krueger, 1990 Krueger et al., 1983, 1984; Tobler et al., 1984 De Sarro et al., 1990 De Sarro et al., 1990 Shoham et al., 1987 Krueger et al., 1982 Krueger et al., 1984; Masek and Kadlec, 1983; Pappenheimer, 1983 Jouvet, 1984; O'Dorisio et al., 1984 Graf and Kastin, 1984; Yehuda et al., 1987 Promoting Wakefulness Reference Inhibiting IL-1 and Sleep Corticotropin-releasing factor ACTH a-MSH Glucocorticoids Krueger, 1990 Krueger, 1990 Krueger, 1990 Krueger, 1990
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From page 464... ...
(Brown et al., 1989; Husband, 1993~. Phase shifts, as they are encountered in shift workers or after transmeridian flights, or rhythm disturbances in people under grossly irregular work schedules lead to internal desynchronization of immune-related circadian rhythms and to impairment of immune functions.
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Sleep deprivation leads to impairment of antibody response (A) and of elimination of antigen (B)
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From page 466... ...
Related to differences in the human immune response during different stages of the menstrual cycle may be the clinical observation of a greatly reduced overall and recurrence-free survival in women with breast cancer who were operated on during days 3 to 12 after onset of menstruation as compared with women operated on between days 0 through 2 or days 13 through 32 (Badwe et al., 1991; Hrushesky and Marz, 1994; Senie et al., 1991~. SEASONAL CHANGES AND/OR CIRCANNUAL VARIATIONS IN IMMUNE RESPONSE Changes of immune-related variables during different seasons may be caused by climatic differences, including day length, temperature, and related factors such as exposure to allergens and microorganisms, but they may also be the consequence of endogenous circannual rhythms that may or may not be synchronized by environmental (climatic and other)
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From page 467... ...
In healthy subjects and in patients with cancer, the circannual variation resulted in relatively low enzyme levels between April and June and higher levels between October and February. Seasonal modifications in immune response must be considered in clinical trials and in the planning of immunotherapeutic treatment strategies for various diseases.
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From page 468... ...
is reached in diurnally active human subjects during the late afternoon (Lundeen et al., 1990; Winget et al., 1994~. Exercise induces changes in the T-cell number, in the relation of CD4+ cells to CD8+ cells, the sensitivity of T-cell ,B-adrenoceptors, INK cell activity, interleukin production, and cell proliferation.
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From page 469... ...
Also the circadian rhythms of many liver enzymes are synchronized primarily by the time of food uptake (Fuller and Snoddy, 1968~. In human subjects, some of the most stable rhythms (such as plasma cortisol and circulating lymphocytes)
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From page 470... ...
, and TSH (Blalock, 1989, 1992; Weigent and Blalock, 1995~. Immune competent cells, including both T- and B-lymphocytes, carry highaffinity receptors for the POMC peptides including ACTH (Clarke and Bost, 1989)
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From page 471... ...
. The large-amplitude circadian rhythm in plasma cortisol concentration in humans with peak values in the early morning hours in diurnally active subjects has been related to changes in immune response, with the minimum in response corresponding to the peak in cortisol concentrations (Lee et al., 1997; Reinberg et al., 1963~.
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From page 472... ...
The circadian variation in plasma PRL concentrations is modulated by sleep but to a lesser degree than that of growth hormone (hGH)
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From page 474... ...
of the biologic rhythms within a frequency range, a disruption of this sequence that results in the right metabolite not being provided at the right time may lead to malfunction and immune deficiencies, as seen during exposures to phase shift, sleep deprivation, severe stress, and other
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From page 475... ...
Seasonal as well as circadian variations in the toxicity of chemotherapeutic agents were found for epirubicin and for doxorubicin (Mormont et al., 1988) , THP (4'-0-tetrahydropyranyladriamycin)
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From page 476... ...
, such as light-darkness, activity-rest pattern, temperature, and for some parameters in human subjects less than in experimental animals, the time of food uptake. · Rhythmic changes in the functional stage of cell and organ systems are predictable in their timing if (1)
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From page 477... ...
· Factors that affect neuroendocrine rhythms also affect immune functions (e.g., sleep and sleep deprivation; physical exercise, moderate or exhaustive; phase shifts; or other rhythm disturbances, including shift work)
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From page 478... ...
I Circadian rhythms of human T-, B-, and K-cell traffic in the peripheral blood.
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From page 479... ...
1981. Circannual variations in the B-cell/T-cell ratio in normal human peripheral blood.
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1978. Circadian variation in an immune response in man.
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1995. Steroids as regulators ofthe mammalian immune response.
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1974. Differences in immune response of mice to sheep red blood cells as a function of circadian phase.
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1976. Timing of single daily meal influences relations among human circadian rhythms in urinary cyclic AMP and hemic glucagon, insulin, and iron.
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1995. Time relation of circadian rhythms in plasma dehydroepiandrosterone and dehydroepiandrosterone-sulfate to ACTH, cortisol, and 11-desoxycortisol-#107 [abstract]
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1982. The effects of the light-dark cycle on humoral and cell-mediated immune responses of mice.
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1993. Role of central nervous system and behavior in the immune response.
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1989. Thyrotropin: An endogenous regulator of the in vitro immune response.
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1988b. Seasonal modulation of the circadian time structure of circulating T- and natural killer lymphocyte subsets from healthy subjects.
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1971. Periodicity during recovery of the immune response after cyclophosphamide treatment.
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1975. Circadian rhythms in mice fed a single daily "meal" at different stages of LD 12:12 lighting regimen.
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1980. Immune responses have rhythms.
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Pp. 243-255 in Biologic Rhythms in Clinical and Laboratory Medicine, 2d ea., Y
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1984. Circannual variation of insulin secretion in clinically healthy subjects in Italy, Romania, and the U.S.A.
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Pp. 453~69 in Biologic Rhythms in Clinical and Laboratory Medicine, 2d ea., Y
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1975. Circadian lymphocytic rhythms in clinically healthy subjects and in patients with hematologic malignancies [abstract]
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From page 496... ...
Pp. 230-242 in Biologic Rhythms in Clinical and Laboratory Medicine, 2d ea., Y
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