Thermoregulation during fever: Change of set-point or change of gain

Mitchell, Duncan; Snellen, J. W.; Atkins, A.R.

doi:10.1007/bf00588644

Cited by 77 publications

(27 citation statements)

References 20 publications

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“…The 'set point' in this system has come to mean the value of some reference signal in the thermoregulatory system and the theory of fever being a change in this is long standing (Atkins, 1964). Others have suggested that the febrile responses are best explained in terms of a change in sensitivity, or gain, in the thermoregulatory centre (Mitchell, Snellen & Atkins, 1970) rather than a change in a reference point. In considering the neural processes in thermoregulation, Hensel (1973) concluded that a change of gain in some thermosensitive structures could account for the change in temperature control during fever.…”

Section: 'Hermoregulation and Fevermentioning

confidence: 99%

The effect of endotoxin‐induced fever on thermoregulation in the newborn rabbit.

Hull

Vinter

McIntyre

1993

The Journal of Physiology

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SUMMARY1. Metabolic responses of endotoxin-injected newborn rabbits were measured in a closed circuit calorimeter at a constant environmental temperature within their thermoneutral range. Oxygen consumption and colonic temperatures were then measured over a range of environmental temperatures from 21-0 to 40 0°C and the responses of endotoxin-injected rabbits compared with non-injected litter mates.2. To measure their preferred thermal environment, endotoxin-injected and noninjected litter mates were allowed to settle on a thermal gradient and their colonic temperatures measured.3. In a constant environmental temperature of 37°C, rises in oxygen consumption and colonic temperature following endotoxin injection were found to be biphasic.Oxygen consumption rose from 21 ml kg-' min-1 to a maximum 35 ml kg-1 minand colonic temperature rose from 39 0 to 39 8 'C.4. The maximal rate of oxygen consumption was the same in both injected and non-injected animals, 53 ml kg-1 min-', being provoked at the same environmental temperature of 24 'C. Minimal rates of oxygen consumption were also similar for the two groups but in the injected animals they were achieved at an environmental temperature of 39°C, 2 'C higher than for non-injected animals.5. We conclude that newborn rabbits challenged with a pyrogen have both behavioural and physiological responses. The thermogenic response is consistent with a change in sensitivity to feedback information rather than a simple shift in the central thermoregulatory set point. We find no evidence to support the view that in the febrile response a higher body temperature necessitates an increase in metabolic rate, the so-called Q1o effect.

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Section: 'Hermoregulation and Fevermentioning

confidence: 99%

The effect of endotoxin‐induced fever on thermoregulation in the newborn rabbit.

Hull

Vinter

McIntyre

1993

The Journal of Physiology

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“…This shift of the regulated variable during fever can be used to study the nature of the system which regulates body temperature. It is generally admitted that the physiological thermostat has the characteristics of a proportional regulator with a set point (Hardy, 1965;Hammel, 1965) but recently Mitchell, Snellen & Atkins (1970) have offered an alternative theory based on changes in the slope of the regressions which describe the relations between electrical activity and tem-M. CABANAC AND B. MIASSONNET perature of hypothalamic temperature sensitive neurones. They have postulated that if warm sensors become less responsive and cold sensors more responsive to temperature changes during fever, this change in slope rather than change in the intercept is indicative of a change in gain of the thermoregulatory system during fever, rather than a change in set-point of the system.…”

Section: Introductionmentioning

confidence: 99%

Temperature regulation during fever: change of set point or change of gain? A tentative answer from a behavioural study in man

Cabanac¹,

Massonnet²

1974

The Journal of Physiology

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SUMMARY1. Four subjects were immersed in a stirred water-bath maintained at either 30 or 400 C. The left hand was placed out of the bath in a glove receiving water at a temperature selected by the subject as most pleasurable. Experiments were conducted during the euthermic state and during either spontaneous or induced fever.2. The results of control experiments confirm a previous observation using the same method, that preferred hand skin temperature was a linear function of internal temperature but also indicated an influence by mean skin temperature.3. The general pattern of response during fever was identical to that when fever was absent except that the regulated steady state internal temperature was higher and the slopes of preferred temperature plotted against internal temperature were steeper.4. The results seem to support the concept of a change in set point rather than that of a change in the gain of the thermoregulatory processes during fever.

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“…The capacity of the body to suppress disturbances-in the model domain represented by the open loop gain of the regulation loop (Peper et al 1988;Peper 2004b)-is of major importance. The latter parameter is not fixed but depends on health and age (Mitchell et al 1970;Verveen 1978Verveen , 1983Peper et al 1987Peper et al , 1988Peper 2004a;). The consequence is that an individual's level of tolerance to a certain drug and the resulting drug effect may appear different in different situations.…”

Section: Sensitization and Other Paradoxical Effectsmentioning

confidence: 99%

Aspects of the Relationship between Drug Dose and Drug Effect

Peper

2009

Dose-Response

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ᮀ It is generally assumed that there exists a well-defined relationship between drug dose and drug effect and that this can be expressed by a dose-response curve. This paper argues that there is no such clear relation and that the dose-response curve provides only limited information about the drug effect. It is demonstrated that tolerance development during the measurement of the dose-response curve may cause major distortion of the curve and it is argued that the curve may only be used to indicate the response to the first administration of a drug, before tolerance has developed. The precise effect of a drug on an individual depends on the dynamic relation between several variables, particularly the level of tolerance, the dose anticipated by the organism and the actual drug dose. Simulations with a previously published mathematical model of drug tolerance demonstrate that the effect of a dose smaller than the dose the organism has developed tolerance to is difficult to predict and may be opposite to the action of the usual dose.

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Thermoregulation during fever: Change of set-point or change of gain

Cited by 77 publications

References 20 publications

The effect of endotoxin‐induced fever on thermoregulation in the newborn rabbit.

The effect of endotoxin‐induced fever on thermoregulation in the newborn rabbit.

Temperature regulation during fever: change of set point or change of gain? A tentative answer from a behavioural study in man

Aspects of the Relationship between Drug Dose and Drug Effect

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