Therapeutic possibilities

Endocrine manipulations

Some therapeutic effect can be observed if animals are treated with a combination of a DHEA metabolite and a glucocorticoid (R. Hernandez-Pando, K. Arriaga, L. Pavon & G. A. W. Rook, unpublished work 1997) intended to mimic the ratio seen during the 'safe school age' (5—10 years) when children are resistant to the

TABLE 1 Suggested correlations between dehydroepiandrosterone (DHEA) levels (or DHEA/glucocorticoid ratios) and immunopathology of tuberculosis in humans at different ages. Manipulating the ratios of glucocorticoid to DHEA in tuberculous mice causes similar changes in pathology

Ratio of glucocorticoid to DHEA in Age (human) DHEAS level Disease type tuberculous mice

TABLE 1 Suggested correlations between dehydroepiandrosterone (DHEA) levels (or DHEA/glucocorticoid ratios) and immunopathology of tuberculosis in humans at different ages. Manipulating the ratios of glucocorticoid to DHEA in tuberculous mice causes similar changes in pathology

Ratio of glucocorticoid to DHEA in Age (human) DHEAS level Disease type tuberculous mice

0—5 years

Low

Consolidation,

Normal mouse, i.e. low DHEA and

pneumonia,

normal corticosterone

no cavitation

5—10 years

-1 ^g/mi

Resistant (safe

Mouse with late tuberculosis treated with

school age)

DHEA and corticosterone

Puberty

~4 ^g/m!

Adult type,

Mouse with late tuberculosis treated with

with necrosis

DHEA but no corticosterone

and cavitation

supplement

DHEAS, sulfated form of DHEA.

DHEAS, sulfated form of DHEA.

disease (Donald et al 1996; Table 1). It is possible that this strategy could help human drug-resistant cases. It is also possible that drugs such as derivatives of glycyrrhetinic acid that can block enzymes of the cortisol/cortisone shuttle would have beneficial effects if reductase activity in the lung were limited.

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