Abstract
Clinical, epidemiological and therapeutic studies indicate that some human depression is associated with proinflammatory cytokines, chronic inflammatory disorders, and inflammation-inducing lifestyle factors. Moreover depression can be induced by administration of proinflammatory cytokines, including IL-2 or IFN-α. However, recent studies in specific pathogen-free (SPF) rodents suggest a different-and potentially contradictory-relationship between immune processes and mental health. These studies suggest that effector T cells specific for central nervous system (CNS) antigens can assist recovery from an array of environmental insults ranging from nerve injury to psychological stress, while in contrast, regulatory T cells (Treg) oppose such recovery. Indeed, some reported effects of this so-called " protective autoimmunity" seem of direct relevance to depressive disorders. These findings pose a dilemma for those intending to manipulate inflammatory pathways as a treatment for depression. Should we administer anti-inflammatory treatments, or should we induce self-reactive T cells? We re-examine the rodent findings and outline immunological peculiarities of SPF rodents, the abnormal properties of their regulatory T cells, and the impact of gut microbiota. We find that " protective autoimmunity" is likely to be relevant only to very clean SPF animals that lack normal levels of activated T cells, CNS T cell traffic and mature Treg. The data indicate that even in SPF models the effectors of beneficial effects are not the proinflammatory autoimmune cells themselves, but rather unidentified regulatory cells. This reinterpretation of findings relevant to " protective autoimmunity" suggests that ongoing, and planned, clinical trials of anti-inflammatory strategies to treat depressive disorders are justified.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 591-601 |
| Number of pages | 11 |
| Journal | Brain, Behavior, and Immunity |
| Volume | 25 |
| Issue number | 4 |
| DOIs | |
| State | Published - May 2011 |
| Externally published | Yes |
Fingerprint
Keywords
- Autoimmunity
- IL-10
- Immunoregulation
- Neuroprotection
- Treg
ASJC Scopus subject areas
- Immunology
- Behavioral Neuroscience
- Endocrine and Autonomic Systems
Cite this
Lymphocytes in neuroprotection, cognition and emotion : Is intolerance really the answer? / Rook, Graham A W; Lowry, Christopher A.; Raison, Charles L.
In: Brain, Behavior, and Immunity, Vol. 25, No. 4, 05.2011, p. 591-601.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lymphocytes in neuroprotection, cognition and emotion
T2 - Is intolerance really the answer?
AU - Rook, Graham A W
AU - Lowry, Christopher A.
AU - Raison, Charles L
PY - 2011/5
Y1 - 2011/5
N2 - Clinical, epidemiological and therapeutic studies indicate that some human depression is associated with proinflammatory cytokines, chronic inflammatory disorders, and inflammation-inducing lifestyle factors. Moreover depression can be induced by administration of proinflammatory cytokines, including IL-2 or IFN-α. However, recent studies in specific pathogen-free (SPF) rodents suggest a different-and potentially contradictory-relationship between immune processes and mental health. These studies suggest that effector T cells specific for central nervous system (CNS) antigens can assist recovery from an array of environmental insults ranging from nerve injury to psychological stress, while in contrast, regulatory T cells (Treg) oppose such recovery. Indeed, some reported effects of this so-called " protective autoimmunity" seem of direct relevance to depressive disorders. These findings pose a dilemma for those intending to manipulate inflammatory pathways as a treatment for depression. Should we administer anti-inflammatory treatments, or should we induce self-reactive T cells? We re-examine the rodent findings and outline immunological peculiarities of SPF rodents, the abnormal properties of their regulatory T cells, and the impact of gut microbiota. We find that " protective autoimmunity" is likely to be relevant only to very clean SPF animals that lack normal levels of activated T cells, CNS T cell traffic and mature Treg. The data indicate that even in SPF models the effectors of beneficial effects are not the proinflammatory autoimmune cells themselves, but rather unidentified regulatory cells. This reinterpretation of findings relevant to " protective autoimmunity" suggests that ongoing, and planned, clinical trials of anti-inflammatory strategies to treat depressive disorders are justified.
AB - Clinical, epidemiological and therapeutic studies indicate that some human depression is associated with proinflammatory cytokines, chronic inflammatory disorders, and inflammation-inducing lifestyle factors. Moreover depression can be induced by administration of proinflammatory cytokines, including IL-2 or IFN-α. However, recent studies in specific pathogen-free (SPF) rodents suggest a different-and potentially contradictory-relationship between immune processes and mental health. These studies suggest that effector T cells specific for central nervous system (CNS) antigens can assist recovery from an array of environmental insults ranging from nerve injury to psychological stress, while in contrast, regulatory T cells (Treg) oppose such recovery. Indeed, some reported effects of this so-called " protective autoimmunity" seem of direct relevance to depressive disorders. These findings pose a dilemma for those intending to manipulate inflammatory pathways as a treatment for depression. Should we administer anti-inflammatory treatments, or should we induce self-reactive T cells? We re-examine the rodent findings and outline immunological peculiarities of SPF rodents, the abnormal properties of their regulatory T cells, and the impact of gut microbiota. We find that " protective autoimmunity" is likely to be relevant only to very clean SPF animals that lack normal levels of activated T cells, CNS T cell traffic and mature Treg. The data indicate that even in SPF models the effectors of beneficial effects are not the proinflammatory autoimmune cells themselves, but rather unidentified regulatory cells. This reinterpretation of findings relevant to " protective autoimmunity" suggests that ongoing, and planned, clinical trials of anti-inflammatory strategies to treat depressive disorders are justified.
KW - Autoimmunity
KW - IL-10
KW - Immunoregulation
KW - Neuroprotection
KW - Treg
UR - http://www.scopus.com/inward/record.url?scp=79954639322&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79954639322&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2010.12.005
DO - 10.1016/j.bbi.2010.12.005
M3 - Article
C2 - 21167931
AN - SCOPUS:79954639322
VL - 25
SP - 591
EP - 601
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
SN - 0889-1591
IS - 4
ER -